Combination of Chinese and Western Medicine to Prevent and Reverse Resistance of Cancer Cells to Anticancer Drugs

  • Xin-bing Sui
  • Tian XieEmail author
Feature Article


Resistance to anticancer drugs is a major problem in oncology, which causes the failure of antitumor treatment. A variety of factors contribute to drug resistance, including drug efflux and metabolism, tumor cell heterogeneity, tumor microenvironment stress-induced genetic or epigenetic alterations in the cancer cells and so on. However, how to circumvent this resistance to improve anticancer efficacy remains to be determined. To circumvent chemotherapeutic resistance, many reversal agents have been developed, but most of them fail in clinical trials due to severe adverse effects. Recently, several natural products have been reported to augment sensitivity or overcome resistance of anticancer chemotherapeutic drugs, including elemene, curcumin, Shenqi Fuzheng Injection (参芪扶正注射液), PHY906, etc. Thus, understanding the novel function of Chinese medicine may allow us to develop a promising therapeutic approach to enhance the effects of anticancer strategies and prevent or overcome their resistance in the treatment of cancer patients.


Chinese medicine Western medicine integrative Chinese and Western medicine resistance anticancer drugs 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


Conflict of Interest

The authors declare no conflict of interest. None of the contents of this manuscript has been previously published or is under consideration elsewhere. All the authors read and approved the final version of the manuscript prior to submission.


  1. 1.
    Parikh AR, Leshchiner I, Elagina L, Goyal L, Levovitz C, Siravegna G, et al. Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat Med 2019;25:1415–1421.CrossRefGoogle Scholar
  2. 2.
    Off-target alterations drive resistance to TRK inhibitors in some cancers. Cancer Discov 2019;9:OF7.Google Scholar
  3. 3.
    Kim SG, Becattini S, Moody TU, Shliaha PV, Littmann ER, Seok R, et al. Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus. Nature 2019;572:665–669.CrossRefGoogle Scholar
  4. 4.
    The Lancet O. Rethinking traditional Chinese medicines for cancer. Lancet Oncol 2015;16:1439.CrossRefGoogle Scholar
  5. 5.
    Efferth T, Li PC, Konkimalla VS, Kaina B. From traditional Chinese medicine to rational cancer therapy. Trends Mol Med 2007;13:353–361.CrossRefGoogle Scholar
  6. 6.
    Luo C, Xu X, Wei X, Feng W, Huang H, Liu H, et al. Natural medicines for the treatment of fatigue: bioactive components, pharmacology, and mechanisms. Pharmacol Res 2019;148:104409.CrossRefGoogle Scholar
  7. 7.
    Liu YX, Bai JX, Li T, Fu XQ, Guo H, Zhu PL, et al. A TCM formula comprising Sophorae Flos and Lonicerae Japonicae Flos alters compositions of immune cells and molecules of the STAT3 pathway in melanoma microenvironment. Pharmacol Res 2019;142:115–126.CrossRefGoogle Scholar
  8. 8.
    Jiao L, Xu J, Sun J, Chen Z, Gong Y, Bi L, et al. Chinese herbal medicine combined with EGFR-TKI in EGFR mutation-positive advanced pulmonary adenocarcinoma (CATLA): a multicenter, randomized, double-blind, placebocontrolled trial. Front Pharmacol 2019;10:732.CrossRefGoogle Scholar
  9. 9.
    Wei C, Yao X, Jiang Z, Wang Y, Zhang D, Chen X, et al. Cordycepin inhibits drug-resistance non-small cell lung cancer progression by activating AMPK signaling pathway. Pharmacol Res 2019;144:79–89.CrossRefGoogle Scholar
  10. 10.
    Lu JJ, Dang YY, Huang M, Xu WS, Chen XP, Wang YT. Anti-cancer properties of terpenoids isolated from Rhizoma curcumae—a review. J Ethnopharmacol 2012;143:406–411.CrossRefGoogle Scholar
  11. 11.
    Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: identification of novel components of turmeric. Mol Nutr Food Res 2013;57:1529–1542.CrossRefGoogle Scholar
  12. 12.
    An YW, Hu G, Yin GP, Zhu JJ, Zhang QW, Wang ZM, et al. Quantitative analysis and discrimination of steamed and non-steamed rhizomes of Curcuma wenyujin by GC-MS and HPLC. J Chromatogr Sci 2014;52:961–970.CrossRefGoogle Scholar
  13. 13.
    Zhai B, Zeng Y, Zeng Z, Zhang N, Li C, Zeng Y, et al. Drug delivery systems for elemene, its main active ingredient beta-elemene, and its derivatives in cancer therapy. Int J Nanomedicine 2018;13:6279–6296.CrossRefGoogle Scholar
  14. 14.
    Zhai B, Zhang N, Han X, Li Q, Zhang M, Chen X, et al. Molecular targets of beta-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: a review. Biomed Pharmacother 2019;114:108812.CrossRefGoogle Scholar
  15. 15.
    Wang X, Liu Z, Sui X, Wu Q, Wang J, Xu C. Elemene Injection as adjunctive treatment to platinum-based chemotherapy in patients with stage III/IV non-small cell lung cancer: a meta-analysis following the PRISMA guidelines. Phytomedicine 2019;59:152787.CrossRefGoogle Scholar
  16. 16.
    Xu XW, Yuan ZZ, Hu WH, Wang XK. Meta-analysis on Elemene Injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer. Chin J Chin Mater Med (Chin) 2013;38:1430–1437.Google Scholar
  17. 17.
    Cheng H, Ge X, Zhuo S, Gao Y, Zhu B, Zhang J, et al. Beta-elemene synergizes with gefitinib to inhibit stemlike phenotypes and progression of lung cancer via downregulating EZH2. Front Pharmacol 2018;9:1413.CrossRefGoogle Scholar
  18. 18.
    Zhou K, Wang L, Cheng R, Liu X, Mao S, Yan Y. Elemene increases autophagic apoptosis and drug sensitivity in human cisplatin (DDP)-resistant lung cancer cell line SPC-A-1/DDP by inducing beclin-1 expression. Oncol Res 2017; May 23 [Epub ahead of print].Google Scholar
  19. 19.
    Lin L, Li L, Chen X, Zeng B, Lin T. Preliminary evaluation of the potential role of beta-elemene in reversing erlotinibresistant human NSCLC A549/ER cells. Oncol Lett 2018;16:3380–3388.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Guo Z, Liu Z, Yue H, Wang J. Beta-elemene increases chemosensitivity to 5-fluorouracil through down-regulating microRNA-191 expression in colorectal carcinoma cells. J Cell Biochem 2018;119:7032–7039.CrossRefGoogle Scholar
  21. 21.
    Huang C, Yu Y. Synergistic cytotoxicity of beta-elemene and cisplatin in gingival squamous cell carcinoma by inhibition of STAT3 signaling pathway. Med Sci Monit 2017;23:1507–1513.CrossRefGoogle Scholar
  22. 22.
    Mu L, Wang T, Chen Y, Tang X, Yuan Y, Zhao Y. Betaelemene enhances the efficacy of gefitinib on glioblastoma multiforme cells through the inhibition of the EGFR signaling pathway. Int J Oncol 2016;49:1427–1436.CrossRefGoogle Scholar
  23. 23.
    Zhang J, Zhang HD, Yao YF, Zhong SL, Zhao JH, Tang JH. Beta-elemene reverses chemoresistance of breast cancer cells by reducing resistance transmission via exosomes. Cell Physiol Biochem 2015;36:2274–2286.CrossRefGoogle Scholar
  24. 24.
    Zhang J, Zhang H, Chen L, Sun DW, Mao CF, Chen W, et al. Beta-elemene reverses chemoresistance of breast cancer via regulating MDR-related microRNA expression. Cell Physiol Biochem 2014;34:2027–2037.CrossRefGoogle Scholar
  25. 25.
    Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol 2007;595:1–75.CrossRefGoogle Scholar
  26. 26.
    Landis-Piwowar KR, Milacic V, Chen D, Yang H, Zhao Y, Chan TH, et al. The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist Updat 2006;9:263–273.CrossRefGoogle Scholar
  27. 27.
    Chen P, Huang HP, Wang Y, Jin J, long WG, Chen K, et al. Curcumin overcome primary gefitinib resistance in nonsmall-cell lung cancer cells through inducing autophagyrelated cell death. J Exp Clin Cancer Res 2019;38:254.CrossRefGoogle Scholar
  28. 28.
    Zhang P, Lai ZL, Chen HF, Zhang M, Wang A, Jia T, et al. Curcumin synergizes with 5-fluorouracil by impairing AMPK/ULK1-dependent autophagy, AKT activity and enhancing apoptosis in colon cancer cells with tumor growth inhibition in xenograft mice. J Exp Clin Cancer Res 2017;36:190.CrossRefGoogle Scholar
  29. 29.
    Roy M, Mukherjee S. Reversal of resistance towards cisplatin by curcumin in cervical cancer cells. Asian Pac J Cancer Prev 2014;15:1403–1410.CrossRefGoogle Scholar
  30. 30.
    Sandur SK, Deorukhkar A, Pandey MK, Pabón AM, Shentu S, Guha S, et al. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys 2009;75:534–542.CrossRefGoogle Scholar
  31. 31.
    Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res 2007;67:3853–3861.CrossRefGoogle Scholar
  32. 32.
    Hu Y, Lu W, Chen G, Zhang H, Jia Y, Wei Y, et al. Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound betaphenylethyl isothiocyanate. Blood 2010;116:2732–2741.CrossRefGoogle Scholar
  33. 33.
    Hasegawa H, Yamada Y, Komiyama K, Hayashi M, Ishibashi M, Sunazuka T, et al. A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B), sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) through 15-deoxy-delta 12, 14 prostaglandin J2 production. Blood 2007;110:1664–1674.CrossRefGoogle Scholar
  34. 34.
    Dong J, Su SY, Wang MY, Zhan Z. Shenqi Fuzheng, an injection concocted from Chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review. J Exp Clin Cancer Res 2010;29:137.CrossRefGoogle Scholar
  35. 35.
    Li S, Xu J, Yao Z, Hu L, Qin Z, Gao H, et al. The roles of breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated proteins (MRPs/ABCCs) in the excretion of cycloicaritin-3-O-glucoronide in UGT1A1-overexpressing HeLa cells. Chem Biol Interact 2018;296:45–56.CrossRefGoogle Scholar
  36. 36.
    Wu L, Cao KX, Ni ZH, Li WD, Chen ZP, Chang HB, et al. Effects of Dahuang Zhechong Pill on doxorubicin-resistant SMMC-7721 xenografts in mice. J Ethnopharmacol 2018;222:71–78.CrossRefGoogle Scholar
  37. 37.
    Lam W, Jiang Z, Guan F, Huang X, Hu R, Wang J, et al. PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci Rep 2015;5:9384.CrossRefGoogle Scholar
  38. 38.
    Pan B, Cheng T, Nan KJ, Qiu GQ, Sun XC. Effect of Fuzheng Yiliu Decoction combined with chemotherapy on patients with intermediate and late stage gastrointestinal cancer. World J Gastroenterol 2005;11:439–442.CrossRefGoogle Scholar

Copyright information

© The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Holistic Integrative Pharmacy Institutes and Comprehensive Cancer Diagnosis and Treatment Centerthe Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal UniversityHangzhouChina
  2. 2.Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang ProvinceHangzhou Normal UniversityHangzhouChina

Personalised recommendations