Summary on Chinese medicine composite formulae potentially used for liver cancer treatment.
Liver cancer is an international problem, especially in Asian countries. It is because that most liver cancers are already late stage when they are diagnosed, and also most liver cancers have various previous chronic liver diseases induced by alcoholic, virus, and steatosis, etc. In recent years, laboratory and clinical studies focusing on liver cancer by Chinese medicine has been extensively studied. What Chinese medicine treatment formalities can be used in liver cancer? How Chinese medicine can be employed in treatment of liver cancer? What Chinese medicine can contribute to liver cancer? To answer these questions in this chapter, we will review and discuss treatment of liver cancer from Chinese medicine’s perspective with scientific evidences as following three parts: (1) Chinese medicine as the source of discovering new treatment for liver cancer, (2) Chinese medicine as a complementary treatment of liver cancer, and (3) to discuss future research and application of Chinese medicine in liver cancer treatment.
- Chinese medicine
- liver cancer
- source of drug discovery
- complementary medicine
- clinical application
Liver cancer is one of the most common malignancies with high morbidity and mortality all over the world. Despite the number of new cases of liver cancer appears to be plateauing, large population size of liver cancer patients, especially in China, still greatly contributes to the global cancer deaths . Hepatocellular carcinoma (HCC) is the most commonly observed histological subgroup of primary liver cancer, accounting for 70–90% of the cases. With a global status quo that 746,000 deaths only in 2012 and 10.1 new cases diagnosed within every 10,000 people, HCC ranks the sixth lethal malignancy and the third leading cause of cancer-related deaths .
Over the past decades, the clinical approaches to treat liver cancer have considerably evolved. Patients can benefit from partial hepatectomy, radiotherapy, systemic or local chemotherapy, liver transplantation, and radiofrequency ablative surgery. Nevertheless, numerous adverse events and dismal outcomes still seriously affect the life quality of patients. On the background of shortcomings, developing improved preventive and therapeutic strategy is urgently necessary.
Considering its low toxicity and high activity, Chinese medicine has been deemed as one of the prominent complementary and alternative approaches in tumor therapy. As unique biomedical and pharmaceutical resources, Chinese medicine owns the ability of providing better treatment for liver cancer, either alone or in integrative way . According to Hong Kong Liver Cancer staging system in a population-based investigation, for patients with Va/Vb (tumor status being early, intermediate or locally advanced), the most frequent treatment was Chinese medicine . Another cohort study in Taiwan reported that Chinese medicine users exhibited significant lower risk to suffer HCC, which supported the application of Chinese medicine into the clinical practice of liver cancer treatment . A recent meta-analysis showed that add-on therapy with Chinese medicine regimens in HCC could reduce side effects, activate tumor responses, and improve overall survival. Moreover, cancer subjects were reported to be more inclined to integrating Chinese medicine regimens with conventional therapies rather than conventional treatment only . In this regard, Chinese medicine has been considered as a potential curative choice of method for controlling the proliferation of liver cancer, and thus improving the quality of life and prolonging overall survival of the patients.
Historically, the medical foundation of Chinese medicine can be traced back to 5000 years ago. With contributions and dedications of Chinese medical people in modern and old times, Chinese medicine has been gradually evolved and accepted by the mainstream society. In particular, accompanying the tide of Chinese immigration and cultural communication, Chinese medicine has been approved worldwide and employed in clinical practice in at least 183 countries . Even though many regions have the regulations imposing restrictions to ensure that Chinese medicine is beneficial to liver cancer patients instead of being harmful to public health, the evidence-based guideline has not been covered every field [8, 9].
However, due to its effective curative outcomes in real life, the usage of Chinese medicine in various forms of single compounds, extracted fractions, and composite formulae has attracted a great deal of attentions over the past few decades. Chinese medicine may be capable of retarding liver cancer progression with its multitargets and coordinated intervention actions, either in combination with conventional therapies or radiation alone. Here, we retrospectively reviewed and analyzed the functional roles of Chinese medicine in the treatment of liver cancer.
2. Chinese medicine as the source of discovering new treatment for liver cancer
As mentioned above, currently there are various therapies for liver neoplasm. However, the overall survival rate of patients still remains unsatisfactory on account of high invasiveness and metastasis, chemotherapeutic resistance, and so on. Chinese medicine, in various forms including composite formulae, extracted fractions, monomers, and their derivatives, has been pursued as ideal and novel sources for therapeutic agent development for cancer.
2.1. Single compounds from Chinese medicine for the treatment of liver cancer
Berberine is a natural product in many Chinese medicinal herbs, especially
Flavonoids commonly exist in Chinese medicine and could be isolated from many different kinds of herbal medicine. In recent years, the precise molecular mechanism underlying the obvious antiliver tumor effect of flavonoids has been studied. For example, hydroxysafflor yellow A (HSYA), a kind of flavonoid extracted from
Brucein D (BD) is an active constituent derived from
Matrine, a chemical component came from the roots of sophora species, mainly
Longikaurin A (LK-A) is a naturally occurring compound of ent-kaurane obtained from
The antitumor of two known pennogenyl saponins, which are derived from
Isoquercitrin was found to strongly repress liver tumor cells via retarding the G1 phase cell cycle and promoting cancer cells apoptosis. In nude mice, the proliferation of transplanted tumors was suppressed after treatment with isoquercitrin. Further study showed that the underlying mechanism might be closely involved in the MAPK and PKC signaling pathways .
Zhang et al. investigated the effect of astragaloside IV (AS-IV) and curcumin on tumor expansion and angiogenesis in nude mice bearing xenografts of HCC. Combining AS-IV and curcumin revealed significant synergistic repressive efficacy against both angiogenic and thrombosis-related factors, which might be mediated by downregulation of
Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid carboxylic acid found among Chinese herbal medicine, has been reported to be a potent component for cancer prevention, including liver cancer. Yie et al. explored the probable mechanisms underlying the antiliver cancer action of UA. Taken together, the results demonstrated that UA inhibited proliferation and induced apoptosis of HCC cells via AMPKα-mediated suppression of Sp1, followed by suppressing DNMT1 expression. The investigation revealed a potential novel mechanism by which UA controlled proliferation of HCC cells, suggesting the critical effect of DNMT1 in HCC chemoprevention and treatment .
Bilobol is a Chinese medical ingredient. Xu et al. identified that bilobol administration could suppress expansion of HepG2 cells, which pretreated with lipopolysaccharide (LPS) to induce inflammation. Bilobol appeared to exhibit antitumor effect via inhibiting the RhoA/ROCK signal transduction during the anti-inflammatory response .
Fucoidan, a sulfated polysaccharide isolated from brown algae, has been applied as an anticancer drug for hundreds of years in Chinese medicine. The results from Zhu et al. revealed that fucoidan had the capacity of antitumor partially through inhibiting the proliferation of HCC cells, although it is unable to repress the angiogenesis induced by HCC . In another study, fucoidan displayed the antimetastatic efficacy on HCC cell lines via upregulating p42/44 MAPK-dependent NDRG-1/CAP43 pathway. Also, fucoidan was found to protect against bile acid-induced hepatocyte apoptosis. This ability suggested fucoidan presented a potent therapeutic agent for HCC treatment .
Telekin is a eudesmane-type sesquiterpene lactone extracted from the natural plant
Gigantol is a phenolic substance derived from the genus Dendrobium. Chen et al. investigated gigantol efficacy on liver cancer cells and the results suggested gigantol inhibited cells expansion and induced apoptosis in HepG2 cells through PI3K/Akt/NF-kappaB signal transduction .
The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) play critical roles in the modulation of cell fate. The two factors even could become potent targets and provide support for the development of antineoplastic agents. Celastrol, one of the triterpene compounds derived from herbal medicine, exerts antitumor effects on various malignancies. Ren et al. demonstrated that for HCC cells, exposure to celastrol led to the sensitivity of the intrinsic apoptotic pathway, at least partly through ER stress and the UPR. Moreover, celastrol was found to repress H22 tumor growth in murine syngeneic model studies by inducing ER stress and apoptosis. These data suggested that targeting ER-stress/UPR was an efficient way for celastrol becoming a potent drug for HCC therapy . Cytisine, a quinolizidine alkaloid, also a major bioactive constituent purified from the
RA-XII, a naturally occurring compound originated from Chinese herbal medicine Rubia yunnanensis, possesses activities of anti-inflammatory and antitumor. Song et al. revealed that RA-XII accelerated apoptosis and repressed protective autophagy via signaling pathway AMPK/mTOR/P70S6K in HepG2 cells, suggesting RA-XII, a cyclopeptide, provides the therapeutic support for potentially being an autophagy inhibitor drug in the therapy of hepatic tumor .
There are many bioactive compounds from Chinese medicine, which are also one part of daily diet. For example,
1,6,7-trihydroxyxanthone (THA) is an active small molecule purified from
An active ingredient cordycepin was extracted from “Dong Chong Xia Cao.” It has been implicated in regulating multiple physiological actions especially antitumor effects. Yao et al. revealed that cordycepin might contribute to tumor progression, EMT, migration, and invasion inhibition in HCC by suppression of signaling pathways E-cadherin and integrin/FAK. Hence, cordycepin is a supplementary candidate or therapeutic agent for preventing liver tumor expansion .
Norcantharidin (NCTD), a small-molecule antitumor drug originated from small animal
Bufalin is the major bioactive constituent of the Chinese medicine Chansu, which is presently employed in clinical practice for cancer therapy. A number of groups have investigated the therapy efficacy of bufalin on hepatoma, either in vivo or in vitro, to explore the therapeutic potential of the drug. Qiu et al. reported that bufalin exhibited considerable antitumor activities in liver cancer cell lines HCCLM3 and HepG2 and the underlying mechanism might be related to the repression of signaling pathway AKT/GSK3β/β-catenin/E-cadherin . Tsai et al. demonstrated that bufalin led to autophagic cell death and G2/M cell cycle phase arrest in SK-HEP-1 HCC cells via activating AKT/mTOR signal transduction pathway . Another group reported that bufalin exerted remarkable antiproliferative activity and apoptosis induction in Huh-7 and HepG-2 cancer cells. Further study supported the prosurvival role of bufalin-induced autophagy when the autophagy pathway was retarded with specific chemical inhibitors, indicating a promising therapeutic approach for HCC therapy combining bufalin with a specific autophagy inhibitor .
In searching for active antihepatoma ingredients from
2.2. Functional roles of Chinese medicine extracts and fractions in liver cancer
Asparagus is not only consumed in daily diet but also employed as an agent in Chinese medicine for multiple types of malignancies therapy. An extract from asparagus, asparagus polysaccharide, has been confirmed to be the major bioactive constituent of asparagus in the respect of antitumor as well as immunity-enhancing activities. In clinical practice, it has been used in a number of malignancies treatment . Weng et al. applied tumor-bearing rat model to systemically evaluate the toxicity and antitumor activity of asparagus polysaccharide and asparagus gel-like material. The results showed a certain tumor inhibitory effect of them via promoting cell apoptosis and suppressing tumor angiogenesis when given as transarterial chemoembolization (TACE) therapy. Meanwhile, it exerted the antihepatoma activity with lower toxic effects as well as reduced kidney and liver functional damage, highlighting its chemotherapeutic potential in clinical application for future liver cancer TACE therapy .
An extract of
Astragalus membranaceus and Salvia miltiorrhiza are medical plants that have been applied for thousands of years in the treatment of liver diseases. According to previous researches, it has showed that these two herbs and their extracts own the ability to inhibit the development liver cancer. Rui et al. investigated that the compound astragalus and salvia miltiorrhiza extract (CASE) could repress diethylinitrosamine-induced hepatoma in rat model via the inhibition of fibrosis and PAI-1 mRNA transcription, indicating the possibility of being development as antihepatoma agents in preventing and treating human liver cancer .
Ethyl acetate extract (EAE) of
Some Chinese medicine scholars have indicated that endogenous wind-evil acted as a critical role in tumor metastasis. On the basis of this, the agent of dispelling wind-evil could serve as a suppressor for cancer metastasis and poor prognosis. Yan et al. observed that scorpion-medicated serum could restrain proliferation, induce apoptosis, as well as inhibit the capacity of migration and invasion in vitro. Further experiments in HCC tumor-bearing metastasis mice models showed that water decoction of scorpion blocked tumor growth and metastasis. More importantly, these results suggested that scorpion, as an important wind calming drug, could inhibit the metastasis and invasion of liver cancer cells especially through epithelial-mesenchymal transition (EMT) reversal, thereby providing a possible potential approach to preventing HCC metastasis .
Ethanol extract of root of
Realgar (As4S4), one of the most useful mineral drugs in Chinese medicine, has been employed in clinical therapy as a potential agent for cancer therapy. However, due to its low solubility and subsequent poor bioavailability, it is difficult to achieve the effective blood medicine dose unless with high dosage of realgar and long period of treatment. A recent study explored realgar transforming solution (RTS) and found the strong antihepatoma activity of RTS via inducing ROS .
2.3. The role of Chinese medicine composite formulae in regressing liver cancer
Huang-lian-jie-du-tang (HLJDT) is oriental medicinal formulation known to possess anti-inflammatory activity. The prescription has been well documented for thousands of years and used for liver protection in Asian community . Recent researches have postulated HLJDT as a regimen for cancer treatment, particularly hepatoma. Hsu et al. found that HLJDT might have an effect on human liver cancer cell lines, Hep G2 and PLC/PRF/5. The results showed that HLJDT significantly triggered cell cycle arrest and contributed to the mitochondrial apoptotic pathway by reducing the level and activity of NF-κB, which suggested that HLJDT might be a promising chemotherapeutic agent without causing cytotoxicity to normal cellular environment . Wang et al. examined the suppressive efficacy of HLJDT on the liver cancer expansion and found that involvement of eEF2 inhibition might be the key mechanism mediating the inhibitory effect of the formula .
Yiguanjian (YGJ), a classic liver-YIN tonifying herbal formula, was established by ancient Chinese medicine practitioner Wei Zhixian in the Qing Dynasty (AD 1722–1772). Researchers optimized the prescription of YGJ on the basis of modern principles in clinical practice of Chinese medicine and then evaluated the antitumor activity of modified YGJ (MYGJ) on Bel-7402 human liver cancer cells. These data showed that MYGJ could interfere proliferation suspension and induce anoikis in cancer cells. The mechanisms underlying the actions of MYGJ might involve in inhibiting the phosphorylation and expression of p38 MAPK, and subsequent regulating intrinsic and extrinsic pathways of apoptosis .
Pien Tze Huang (PZH) is an extensively employed prescription in the treatment of multiple malignancies and has possible therapeutic effects in clinical therapy for HCC. Qi et al. aimed to elucidate the efficacy of PZH on the proliferation and apoptosis of liver cancer cell lines and demonstrated PZH could effectively inhibit cancer cell proliferation and induce apoptosis in Bel-7402 HCC cells by upregulating miR-16, which has been verified as tumor suppressor, suggesting a novel potential therapeutic for HCC patients .
Sini-San (SNS) has been employed for the treatment of various types of liver disease. This formulation comprises four prescriptions of Chinese herbal medicine and was first described in “Shanghan Lun (Treatise on Cold Damage Disorders or the Treatise on Cold Injury),” established by one of the most famous ancient Chinese physicians, Zhang Zhongjing (150–219 AD). SNS has shown significant inhibition on tumor growth in HepG2 xenograft model. Lin et al. elucidated the molecular mechanism by which SNS exerted an antimigratory and anti-invasive effect on HBx-activated liver cancer cells. These results showed that SNS suppressed invasiveness and metastasis in HCC cells via multiple signal transduction pathways including downregulating PI3K/Akt, decreasing MAPK and IκB signaling, inhibiting NF-κB and AP-1 activity, and reducing MMP-9 expression. Thus, SNS might be helpful to interfere the invasion and metastasis of HCC .
Songyou Yin (SYY), a composite formula, showed efficacy to repress tumor proliferation, metastasis, and recurrence. An interesting study explored that SYY combining with moderate swimming has potent effect on retraining tumor growth and metastasis mainly via enhancing immune function .
Niu-Huang-Shen (NHS) has been accepted and used in China for a long time with its various effects such as antipyretic, anti-inflammatory, and vasodilatation effects. It was showed that NHS inhibited cell cycle arrest, induced cell apoptosis, and then repressed cell proliferation and invasion, probably through the significant suppression of Yes-associated protein (YAP) expression. NHS may have the therapeutic potential for treating HCC more effectively .
Shuihonghuazi formula (SHHZF) has been employed for early stage of liver cancer in clinical therapy for a long time; a study was designed to investigate potent effects of SHHZF on hepatoma and its metabolomic profiles. The results elucidated that SHHZF exerted inhibitory effects against liver cancer by adjusting the activities of PE N-methyl transferase, lysophospholipase D, methylenetetrahydrofolate reductase, and lysophospholipase .
3. Chinese medicine as a complementary treatment of liver cancer
Chinese medicine is appreciated for its 5000-year-old history and still holds a prominent position in primary health care in China. Chinese medicine could complement Western medicine by using modern techniques; thus, increasing interests in Chinese medicine has been observed over the Western world. In Chinese medicine, a wide range of ingredients have been proven to achieve various effects in cancer therapy, including alleviating the toxicity to human body, retraining tumor metastasis and recurrence, enhancing chemo- or radio-therapeutic effects, and subsequent improving the general status of patients and extending their survival time.
Long-term food restriction and diarrhea may be an adverse factor for liver cancer. Jian-pi-jie-du decoction (JPJD) could improve the quality of life of hepatoma subjects, in particular, the symptoms of diarrhea and decreased food intake. A research indicated JPJD could improve the condition of tumor-bearing rats, which were pretreated with diarrhea and food restriction by increasing ABCC2 expressional level and downregulating the OATP1B2 in liver normal tissues while downregulating ABCC2 as well as upregulating OATP1B2 in cancer tissues .
In terms of radioprotective and radiosensitizing functions of Chinese medicine, a series of concerning studies have been conducted. Numerous Chinese medicine agents have been confirmed to strengthen the therapeutic gain of radiotherapy by the way of serving as radioprotectors for healthy cells or as radiosensitizers for cancer cells [80, 81]. Botanical agents are comprised of multiple phytochemical compounds that may work synergistically or even individually, not only exhibiting favorable therapeutic effects, but also with safety profiles and lower toxicity .
Kou et al. investigated the radiosensitizing effects of ultrafiltration extract of Radix Angelicae Sinensis-Radix Hedysari (RAS-RH) in human hepatoma cells. The results reported that the RAS-RH significantly enhanced the radiosensitivity of H22 cells of 12C6+ heavy ion radiation. Further study explored the underlying mechanism of radiosensitization, which is to increase caspase-dependent apoptosis via reducing surviving expressional level, suggesting a promising potent radiosensitizer .
Zhang et al. demonstrated that a flavonoid dihydromyricetin (DHM) exerted anticancer activity against hepatoma cells as well as xenotransplanted tumors in nude mice by activating the p53-dependent apoptosis pathway. And best of all, DHM was indicated to play a prominent role when administered in combination with cisplatin . In this case, DHM could be an ideal anticancer drug with minimal side effects because it can alleviate cytotoxicity caused by cisplatin in normal liver cells.
Some studies investigated the adjunctive role of bufalin in reversal chemoresistance in the treatment of liver cancer. The Akt activation triggered by sorafenib is regarded to be responsible for this resistant phenomenon. Zhai et al. investigated that bufalin had the ability of reversing both inherent and acquired resistance to sorafenib via the IRE1 pathway in an ER-stress-dependent manner. These data warranted further studies to examine the utility of bufalin in combination with sorafenib as a first- or second-line treatment after sorafenib alone gains failure in advanced liver cancer . Fluorouracil (5-FU) is a type of anticancer chemotherapeutics, which has been used for 40 years in clinical practice. A research confirmed the reversal effect of bufalin on drug resistance in a moderate multidrug resistance cell line Bel-7402/5-FU. They found Bufalin could block the cell cycle at G0/G1 phase, induce apoptosis through an increase of Bax/Bcl-xL ratio, inhibit the drug efflux pump activity via downregulation of MRP1, and reduce the expression of thymidylate synthase in vitro. All these data revealed that in Bel-7402/5-FU cells, the combination of bufalin with cytotoxic drugs could considerably reverse the MDR through multiple pathways including cell cycle arrest, apoptosis induction, etc., indicating an effective strategy for the chemotherapy of HCC .
Xu et al. investigated the efficacy of drug combination of luteolin and 5-FU on the proliferation of HepG2 and Bel-7402 cells. The data showed that luteolin synergized 5-FU at different dose ratios and then exerted the antitumor effects against HCC cells. Potential mechanism for synergistic effects may be associated with apoptosis and 5-FU metabolism, as evidenced by the increased bax/bcl-2 ratios, upregulated p53 expressions, and induced PARP cleavage .
ADCX, a natural cycloartane triterpenoid isolated from
Arsenic trioxide (As2O3) with high doses is employed to treat solid tumors and acute promyelocytic leukemia, which mostly induce toxic side effects to healthy cells. Andrographolide is a kind of Chinese medicine that exhibits various effects against diseases such as anti-inflammatory, antivirus, antitumor, and so on. Duan et al. demonstrated that andrographolide enhanced As2O3-induced apoptosis in a caspase-3-dependent manner via downregulation of EphB4 in HCC cells. These findings suggested that lower concentrations of As2O3 in combination with andrographolide could be used as chemotherapy for HCC with the potential to minimize the adverse events from As2O3 treatment alone .
The aqueous extract of
A recent research was performed to explore the combination effect of Huaier aqueous extract and chemotherapeutic agent cisplatin or rapamycin. The findings showed that Huaier had the capacity of activating mTOR signaling, which contributed to the enhanced cancer cells sensitivity to chemotherapeutics in response to Huaier administration. Huaier, thus, can potentially be used in integrated chemotherapy with rapamycin or cisplatin for liver cancer therapy .
Cinobufacini, a mixture of a number of components in Chinese medicine, has been used extensively for HCC therapy with strong apoptosis-inducing activity. Xia et al. used a combination of doxorubicin with cinobufacini to achieve tumor-suppression efficiency and found the combination group had a more considerable apoptotic effect by affecting proteins and RNA of apoptosis-related elements, such as Bcl-2, Bax, Bid, and cytochrome C. Consequently, cinobufacini in combination with chemotherapeutic agents might be a new strategy to improve the treatment effect for HCC patients .
Shufeng Jiedu Capsule (SFJDC) has been widely used due to its various pharmacological actions such as anti-inflammation, antibacterial, antiviral, and antitumor. Recently, scholars used combination of SFJDC with doxorubicin to treat liver cancer cells and further explored the underlying mechanisms of SFJDC as well as its constituents in vitro. The data showed that the combination group induced more considerable apoptosis and invasion and migration suppression than control group by targeting NF-κB, Akt/mTOR, and mitochondrial signaling pathways .
Dahuang zhechong pill (DHZCP) is one of the most famous prescriptions from an ancient Chinese medical classic “Jin Kui Yao Lue (Essential Prescriptions from the Golden Cabinet).” DHZCP is officially recorded in the Chinese Pharmacopeia and is commonly used for clinical practice of hepatoma. Wu et al. found that inhibitory growth of doxorubicin-resistant HCC subcutaneous xenografts in nude mice was achieved by DHZCP, and apoptosis promotion was accelerated by doxorubicin. The reversal of doxorubicin resistance by DHZCP was related with energy metabolism decline and regulation of proapoptotic proteins expression .
Accumulating researches have demonstrated that Chinese medicine is a promising substitute for therapy of liver cancer. Furthermore, increasing scholars starts to pay attention to clinical studies of Chinese medicine. For example, gambogic acid (GA), a naturally occurring compound from ancient China, has been demonstrated efficient antineoplastic activity in a number of malignancies. More importantly, it has entered phase II clinical trials. A team ?found GA might lead to oxidative stress and subsequently induce apoptosis in hepatoma cells through interacting with TrxR1. Thus, targeting TrxR1 by GA disclosed a previously unrecognized mechanism underlying the biological action of GA and provides useful information for further development of GA as a potential agent for cancer therapy . On the other hand, the theory of “Jianpi Huayu Therapy” (JPHY) was rooted from “Jin Kui Yao Lue.” According to the selection criteria, Zhong et al. recruited a total of 120 patients in a randomized trial, aiming to compare the curative outcome and safety profile of surgery in combination with “Jianpi Huayu Therapy” HCC treatment to surgery alone. The patients in treatment group received the basic prescription based on JPHY. The results showed that hepatectomy combined with JPHY was more effective with reducing postoperative metastasis and recurrence and prolonged overall survival of HCC patients . JQ1, one of the bromodomain and extra-terminal domain (BET) inhibitors, has been emerged as a novel agent candidate for cancer treatment in clinical research. Nevertheless, a number of solid cancers are resistant to BET inhibitors. The results from a group showed that oridonin synergistically increased JQ1 capacity of inhibiting HCC cell survival, and considerably enhanced JQ1-caused apoptosis in HCC cells and in HCC cancer stem-like cells. Furthermore, they demonstrated that oridonin distinctly augmented the sensitivity of JQ1 via downregulation of the level of multiple antiapoptotic proteins, including Bcl-2, Mcl-1, and x-linked inhibitor of apoptosis, suggesting that the combination treatment of JQ1 and oridonin could be further pursued for clinical application and it was expected to provide a rational for HCC tumor prevention .
Collectively, the aforementioned findings showed the potential efficacy of Chinese medicine on numerous types of cancer, either alone or in combination with conventional treatment of method such as surgery, chemotherapy, or radiation. In particular, as stated above, when integrated with chemotherapy or radiotherapy, Chinese medicine may serve as complementary drugs strongly enhancing the positive effects or reducing the negative events induced by radiochemotherapy. However, in comparison with a great deal of laboratory researches, clinical trials still remain poor, which limits the wide application of Chinese medicine throughout the world.
Chinese medicine is increasingly emerging as a novel curative choice for liver cancer. This retrospective review systemically introduced and evaluated the functional roles of Chinese medicine in treating liver cancer. Chinese medicine has potentially exerted efficient anticancer properties. For example, liver cancer progression can be repressed by active constituents derived from Chinese medicine through multiple pathways. The specific network with regard to the potential therapeutic targets for liver cancer treatment was constructed (Figure 1). The detailed relationships between biological factors and refined extracts could be directly visualized in Figure 1. Moreover, composite formulae as promising curative are increasingly indispensable in current clinical practice. As summarized in Table 1, formulae potentially employed in practice were studied in laboratory and the regulatory mechanisms for the treatment of liver cancer have been showed clearly. Also, Chinese medicine may serve as adjuvant agents in surgery as well as in combination with conventional radio- and chemotherapy, to decrease the adverse events or enhance the treatment outcome. Taken all together, Chinese medicine possesses the potential in liver cancer treatment, and rational application in clinical therapy needs to be warranted in the future.
|Huang-lian-jie-du-tang||Cell cycle arrest, induce mitochondrial apoptotic pathway, inhibit HCC cell proliferation, suppress growth and angiogenesis in xenografted murine model||[71, 72]|
|Yiguanjian||Interfere proliferation suspension and induce anoikis in cancer cells|||
|Pien Tze Huang||Inhibit cancer cell proliferation and induce apoptosis|||
|Sini-San||Suppressed invasiveness and metastasis in HCC cells|||
|Songyou Yin||Repress tumor proliferation, metastasis, and recurrence|||
|Niu-Huang-Shen||Cell cycle arrest, induce cell apoptosis, and cell invasion|||
|Shuihonghuazi formula||Increase the uptake and utilization of linoleic acid and oleic acid, increase arachidonic acid-like substance content, and enhance organism immunity of liver cancer rats|||
|Jian-pi-jie-du decoction||Improve the condition of tumor-bearing rats with the symptoms of diarrhea and decreased food intake|||
|Cinobufacini||Combination of doxorubicin with cinobufacini to achieve a more considerable apoptotic effect|||
|Shufeng Jiedu Capsule||Combination of SFJDC with doxorubicin induced more considerable apoptosis and invasion and migration suppression|||
|Dahuang zhechong pill||Inhibit growth of doxorubicin-resistant HCC subcutaneous xenografts in nude mice and accelerate apoptosis promotion integration with doxorubicin|||
The study was financially supported by grants from the research council of the University of Hong Kong (project codes: 104004092, 104004460, 104004746), the Research Grants Committee (RGC) of Hong Kong, HKSAR (project codes: 764708, 766211, 17152116), Wong’s Donation on Modern Oncology of Chinese Medicine (project code: 200006276), and Gala Family Trust (project code: 200007008).