Traditional Chinese medicine (TCM) combined with chemotherapy drugs has shown promising potential in enhancing efficacy and reducing toxicity in the treatment of colorectal cancer, yet its pharmacological mechanisms remain to be systematically elucidated. On the one hand, TCM enhances chemotherapeutic efficacy directly or indirectly through four pathways: regulating cell cycle progression, inducing autophagy and apoptosis, reversing multidrug resistance, and remodeling the immune microenvironment. On the other hand, it exerts toxicity-attenuating effects via anti-inflammatory and antioxidant mechanisms, including repairing nerve damage, promoting recovery of bone marrow hematopoietic function, and maintaining intestinal mucosal barrier integrity. This article systematically reviews mechanistic studies and clinical research on the combination of TCM formulas, single herbs, and their active ingredients with chemotherapeutic agents, and discusses the limitations of current research as well as future development directions, aiming to provide a reference for the construction of integrative Chinese and Western medicine treatment models.

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

2. Benson AB, Venook AP, Adam M, et al. Colon cancer, version 3. 2024, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2024, 22(2D): e240029. DOI: 10.6004/jnccn.2024.0029.

3. Letai A, de The H. Conventional chemotherapy: millions of cures, unresolved therapeutic index[J]. Nat Rev Cancer, 2025, 25(3): 209-218. DOI: 10.1038/S41568-024-00778-4.

4. Ingrand I, Defossez G, Lafay-Chebassier C, et al. Serious adverse effects occurring after chemotherapy: a general cancer registry-based incidence survey[J]. Br J Clin Pharmacol, 2020, 86(4): 711-722. DOI: 10.1111/bcp.14159.

5. Liao S, Jia X, Yang Y, et al. Efficacy and safety of traditional Chinese medicine decoction combined with chemotherapy in the treatment of advanced colorectal cancer: a protocol of a systematic review and Meta-analysis[J]. Medi-cine(Baltimore), 2021, 100(3): e23952. DOI: 10.1097/MD.0000000000023952.

6. Wu J, Liu Y, Fang C, et al. Traditional Chinese medicine preparation combined therapy may improve chemotherapy efficacy: a systematic review and Meta-analysis[J]. Evid Based Complement Alternat Med, 2019, 2019: 5015824. DOI: 10.1155/2019/5015824.

7. Ni B, Xue K, Wang J, et al. Integrating Chinese medicine into mainstream cancer therapies: a promising future[J]. Front Oncol, 2024, 14: 1412370. DOI: 10.3389/fonc.2024.1412370.

8. Wan J, Yao H, Zhang C, et al. Red American ginseng enhances the effect of fluorouracil on human colon cancer cells via both paraptosis and apoptosis pathways[J]. J Appl Biomed, 2018, 16(4): 311-319. https://pubmed.ncbi.nlm.nih.gov/30976156/

9. Liu H, Liu H, Zhou Z, et al. Herbal formula Huang Qin Ge Gen Tang enhances 5-fluorouracil antitumor activity through modulation of the E2F1/TS pathway[J]. Cell Commun Signal, 2018, 16(1): 7. DOI: 10.1186/s12964-018-0218-1.

10. 王丽, 李芳, 谷妮妮, 等. 羟基红花黄色素A通过Akt/mTOR-自噬通路抑制结直肠癌细胞增殖迁移和化疗耐药[J]. 中国中药杂志, 2023, 48(2): 517-524. [Wang L, Li F, Gu NN, et al. Hydroxysafflor yellow A inhibits proliferation, migration, and chemoresistance of colorectal cancer cells through Akt/mTOR-autophagy pathway[J]. China Journal of Chinese Materia Medica 2023, 48(2): 517-524.] DOI: 10.19540/j.cnki.cjcmm.20221014.703.

11. 孙艳华, 徐建立, 李明, 等. 紫草素对人大肠癌HT29细胞化疗增敏作用研究[J]. 中医学报, 2021, 36(2): 361-365. [Sun YH, Xu JL, Li M, et al. Sensitizing effects of shikonin on human colorectal cancer HT29 cells in chemotherapy[J]. China Journal of Chinese Medicine, 2021, 36(2): 361-365.] DOI:10.16368/j.issn.1674-8999.2021.02.077.

12. 陆曲折, 罗永有, 王鑫, 等. 黄芪多糖通过miR-10b-5p/AGPAT3分子轴调控结直肠癌细胞顺铂耐药性[J]. 沈阳药科大学学报, 2022, 39(8): 970-978. [Lu QZ, Luo YY, Wang X, et al. Astragalus polysaccharide regulates cisplatin resistance in colorectal cancer cells through miR-10b-5p/AGPAT3 molecular axis[J]. Journal of Shenyang Pharmaceutical University, 2022, 39(8): 970-978.] DOI: 10.14066/j.cnki.cn21-1349/r.2020.0982

13. Han W, Yin H, Ma H, et al. Curcumin regulates ERCC1 expression and enhances oxaliplatin sensitivity in resistant colorectal cancer cells through its effects on miR-409-3p[J]. Evid Based Complement Alternat Med, 2020, 2020: 8394574. DOI: 10.1155/2020/8394574.

14. 王丽, 庞静, 沈慧, 等. 白藜芦醇通过EGFR/AKT/mTOR通路改善结直肠癌细胞伊立替康化疗耐药性[J]. 中国药理学通报, 2023, 39(12): 2280-2287. [Wang L, Pang J, Shen H, et al. Resveratrol ameliorates irinotecan chemoresistance of colorectal cancer cells by down-regulating EGFR/AKT/mTOR signaling pathway[J]. Chinese Pharmacological Bulletin, 2023, 39(12): 2280-2287.] DOI: 10.12360/CPB202303020.

15. Wu H, Du J, Li C, et al. Kaempferol can reverse the 5-fu resistance of colorectal cancer cells by inhibiting PKM2-mediated glycolysis[J]. Int J Mol Sci, 2022, 23(7): 3544. DOI: 10.3390/ijms23073544.

16. Su P, Yang Y, Wang G, et al. Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells[J]. Int J Oncol, 2018, 53(3): 1343-1353. DOI: 10.3892/ijo.2018.4461.

17. Pan D, Zhang W, Zhang N, et al. Oxymatrine synergistically enhances doxorubicin anticancer effects in colorectal cancer[J]. Front Pharmacol, 2021, 12: 673432. DOI: 10.3389/fphar.2021.673432

18. Yin J, Wang L, Wang Y, et al. Curcumin reverses oxaliplatin resistance in human colorectal cancer via regulation of TGF-β/Smad2/3 signaling pathway[J]. Onco Targets Ther, 2019, 12: 3893-3903. DOI: 10.2147/OTT.S199601.

19. Deng H, Liu S, Li D, et al. Investigating the pharmacological mechanism of Zhengyuan jiaonang for treating colorectal cancer via network pharmacology analysis and experimental verification[J]. J Ethnopharmacol, 2024, 322: 117607. DOI: 10.1016/j.jep.2023.117607.

20. Hao D, Liu J, Guo Z, et al. Supercritical fluid extract of Angelica sinensis promotes the anti-colorectal cancer effect of oxaliplatin[J]. Front Pharmacol, 2022, 13: 1007623. DOI: 10.3389/fphar.2022.1007623.

21. 王开平, 王瑞童, 韦广燕, 等. 参芪汤联合化疗治疗结直肠癌对免疫蛋白因子、自噬蛋白的多层次影响研究[J]. 中华中医药学刊, 2025, 43(10): 71-75. [Wang KP, Wang RT, Wei GY, et al. Multilevel effect of Shenqi Decoction combined with chemotherapy on immune protein factor and autophagy protein in the treatment of colorectal cancer[J]. Chinese Journal of Traditional Chinese Medicine , 2025, 43(10): 71-75.] DOI: 10.13193/j.issn.1673-7717.2025.10.015.

22. 程权, 石占利, 王硕, 等. 扶正康复合剂对肝郁脾虚型晚期结直肠癌二线化疗患者癌因性疲乏的临床疗效及对肠道菌群的影响[J]. 中药材, 2024, 47(1): 214-219. [Cheng Q, Shi ZL, Wang S, et al. Effect of Fuzheng Kangfu mixture on cancer-related fatigue and intestinal flora in patients with advanced colorectal cancer of liver stagnation and spleen deficiency after second-line chemotherapy[J]. Chinese Materia Medica, 2024, 47(1): 214-219.] DOI: 10.13863/j.issn1001-4454.2024.01.036.

23. Langeh U, Kumar V, Singh C, et al. Drug-herb combination therapy in cancer management[J]. Mol Biol Rep, 2022, 49(11): 11009-11024. DOI: 10.1007/s11033-022-07861-9.

24. Niu X, You Q, Hou K, et al. Autophagy in cancer development, immune evasion, and drug resistance[J]. Drug Resist Updat, 2025, 78: 101170. DOI: 10.1016/j.drup.2024.101170.

25. Zhao R, Zheng S, Li Y, et al. As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy[J]. J Appl Biomed, 2023, 21(1): 23-35. DOI: 10.32725/jab.2022.019.

26. Peng Y, Wang Y, Zhou C, et al. PI3K/Akt/mTOR pathway and its role in cancer therapeutics: are we making headway?[J]. Front Oncol, 2022, 12: 819128. DOI: 10.3389/fonc.2022.819128.

27. Yang Y, Jiang H, Li W, et al. FOXM1/DVL2/Snail axis drives metastasis and chemoresistance of colorectal cancer[J]. Aging(Albany NY), 2020, 12(23): 24424-24440. DOI: 10.18632/aging.202300.

28. 陈勇, 林久茂. 大肠癌多药耐药机制及中药逆转作用的研究进展[J]. 时珍国医国药, 2022, 33(12): 2996-3000. [Chen Y, Lin JM. Research progress on multidrug resistance mechanism of colorectal cancer and reversal effect of traditional Chinese medicine[J]. Lishizhen Medicine and Materia Medica Research, 2022, 33(12): 2996-3000.] DOI: 10.3969/j.issn.1008-0805.2022.12.49.

29. Alsaab HO, Abdullaev B, Alkhafaji AT, et al. A comprehension of signaling pathways and drug resistance; an insight into the correlation between microRNAs and cancer[J]. Pathol Res Pract, 2023, 251: 154848. DOI: 10.1016/j.prp.2023.154848.

30. Gao L, Wu ZX, Assaraf YG, et al. Overcoming anti-cancer drug resistance via restoration of tumor suppressor gene function[J]. Drug Resist Updat, 2021, 57: 100770. DOI: 10.1016/j.drup.2021.100770.

31. Ma L, Zong X. Metabolic symbiosis in chemoresistance: refocusing the role of aerobic glycolysis[J]. Front Oncol, 2020, 10: 5. DOI: 10.3389/fonc.2020.00005.

32. Rezayatmand H, Razmkhah M, Razeghian-Jahromi I. Drug resistance in cancer therapy: the pandora's box of cancer stem cells[J]. Stem Cell Res Ther, 2022, 13(1): 181. DOI: 10.1186/s13287-022-02856-6.

33. Luo W, Shi Q, Han M, et al. TGF-β-driven EMT in cancer progression and drug resistance[J]. Cytokine Growth Factor Rev, 2025, 85: 11-25. DOI: 10.1016/j.cytogfr.2025.05.004.

34. 曹迪, 张亚密, 全建峰. 中医药改善化疗毒副反应的研究进展[J]. 中国中医急症, 2020, 29(7): 1302-1305. [Cao D, Zhang YM, Quan JF. Research progress on the improvement of chemotherapy side effects by traditional Chinese medicine[J]. Journal of Emergency in Traditional Chinese Medicine, 2020, 29(7): 1302-1305. ] DOI: 10.3969/j.issn.1004-745X.2020.07.052.

35. Behranvand N, Nasri F, Zolfaghari Emameh R, et al. Chemotherapy: a double-edged sword in cancer treatment[J]. Cancer Immunol Immunother, 2022, 71(3): 507-526. DOI: 10.1007/s00262-021-03013-3.

36. Uhelski ML, Li Y, Fonseca MM, et al. Role of innate immunity in chemotherapy-induced peripheral neuropathy[J]. Neurosci Lett, 2021, 755: 135941. DOI: 10.1016/j.neulet.2021.135941.

37. Tan W, Pan T, Wang S, et al. Immunometabolism modulation, a new trick of edible and medicinal plants in cancer treatment[J]. Food Chem, 2022, 376: 131860. DOI: 10.1016/j.foodchem.2021.131860.

38. Zouein J, Haddad FG, Eid R, et al. The combination of immune checkpoint inhibitors and chemotherapy in advanced non-small-cell lung cancer: the rational choice[J]. Immunotherapy, 2022, 14(2): 155-167. DOI: 10.2217/imt-2021-0014.

39. Lee E, Yang J, Choi J, et al. Augmented antitumor effect of unripe rubus coreanus miquel combined with oxaliplatin in a humanized PD-1/PD-L1 knock-in colorectal cancer mouse model[J]. Cells, 2022, 11(18): 2876. DOI: 10.3390/cells11182876.

40. 李瑞晓, 李琦, 季青. 肠道菌群对肿瘤免疫的影响及中医药干预研究[J]. 中华中医药杂志, 2020, 35(6): 2999-3002. [Li RX, Li Q, Ji Q. Study on the effects of intestinal flora on tumor immunity and intervention of traditional Chinese medicine[J]. Chinese Journal of Traditional Chinese Medicine 2020, 35(6): 2999-3002]. https://d.wanfangdata.com.cn/periodical/ChdQZXJpb2RpY2FsQ0hJU29scjlRdWljaxIPemd5eXhiMjAyMDA2MDgyGghlbjlwZmp6bA%3D%3D.

41. Pacheco C, Baião A, Ding T, et al. Recent advances in long-acting drug delivery systems for anticancer drug[J]. Adv Drug Deliv Rev, 2023, 194: 114724. DOI: 10.1016/j.addr.2023.114724.

42. Zhang Q, Liu J, Duan H, et al. Activation of Nrf2/HO-1 signaling: an important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress[J]. J Adv Res, 2021, 34: 43-63. DOI: 10.1016/j.jare.2021.06.023.

43. Yang YL, He ZZ, Wu SC. Ursolic acid alleviates paclitaxel-induced peripheral neuropathy through PPARγ activation[J]. Toxicol Appl Pharmacol, 2024, 484: 116883. DOI: 10.1016/j.taap.2024.116883.

44. 初秋博. 基于免疫调控的贞芪扶正颗粒促造血及抗结直肠癌活性的研究[D]. 长春: 吉林大学, 2020. DOI: 10.27162/d.cnki.gjlin.2020.000033.

45. 王若进, 李绍旦, 王朴, 等. 加减圣愈汤改善晚期结肠癌患者肿瘤化疗相关性中度贫血的临床研究[J]. 中医药导报, 2021, 27(2): 49-52, 59. [Wang RJ, Li SD, Wang P, et al. Clinical study on Modified Shengyu Decoction in improving moderate anemia related to tumor chemotherapy in patients with advanced colon cancer[J]. Chinese Medicine Review, 2021, 27(2): 49-52, 59.] DOI: 10.13862/j.cnki.cn43-1446/r.2021.02.012.

46. 徐露, 王娴, 王宣璎, 等. 姜黄素介导IL-6/STAT3信号通路修复结肠癌5-FU化疗引起的肠黏膜损伤[J]. 中国中药杂志, 2021, 46(3): 670-677. [Xu L, Wang X, Wang XY, et al. Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy in colon cancer[J]. Chinese Journal of Traditional Chinese Medicine, 2021, 46(3): 670-677.] DOI: 10.19540/j.cnki.cjcmm.20201106.401.

47. 周张杰, 蒋海燕, 钟薏, 等. 健脾固肠方通过提高短链脂肪酸产生菌的丰度减轻肠癌小鼠化疗后肠道炎症反应的机制探讨[J]. 中国中医基础医学杂志, 2020, 26(5): 618-621, 632. [Zhou ZJ, Jiang HY, Zhong Y, et al. Effect of Jianpi Guchang recipe on intestinal inflammatory response after chemotherapy in intestinal carcinoma mice by enhancing abundance of short-chain fatty acid producing bacteria[J]. China Journal of Basic Medicine of Traditional Chinese Medicine, 2020, 26(5): 618-621,632.].https://d.wanfangdata.com.cn/periodical/ChdQZXJpb2RpY2FsQ0hJU29scjlRdWljaxIRemd6eWpjeXgyMDIwMDUwMjEaCG1tZXpyaGZy.

48. 崔庆丽, 胡彦辉, 崔庆安, 等. 人参健脾丸治疗伊立替康所致迟发性腹泻及对肠道菌群和血清炎症因子的影响[J]. 中医药学报, 2021, 49(5): 83-86. [Cui QL, Hu YH, Cui QA, et al. Effect of Renshen Jianpi pill on intestinal flora and serum inflammatory factors in treating delayed-onset diarrhea caused by irinotecan[J]. Chinese Journal of Traditional Chinese Medicine, 2021, 49(5): 83-86. ] DOI: 10.19664/j.cnki.1002-2392.210119.

49. 曹鹏, 李松林, 霍介格. 奥沙利铂相关性周围神经病变以血痹论治析[J]. 中国中医基础医学杂志, 2013, 19(4): 430-431. [Cao P, Li SL, Huo JG. Treatment of oxaliplatin-related peripheral neuropathy with blood-arthralgia[J]. China Journal of Basic Medicine of Traditional Chinese Medicine, 2013, 19(4): 430-431.] DOI: 10.19945/j.cnki.issn.1006-3250.2013.04.035.

50. Gu JL, Wei GL, Ma YZ, et al. Exploring the possible mechanism and drug targets of Huang-Qi-Gui-Zhi-Wu-Wu decoction for the treatment of chemotherapy-induced peripheral neuropathy on network pharmacology[J]. Evid Based Complement Alternat Med, 2020, 2020: 2363262. DOI: 10.1155/2020/2363262.

51. Shih YW, Wang MH, Monsen KA, et al. Effectiveness of acupuncture for relieving chemotherapy-induced bone marrow suppression: a systematic review with a Meta-analysis and trial sequential analysis[J]. J Integr Complement Med, 2023, 29(10): 621-636. DOI: 10.1089/jicm.2022.0735.

52. 张江涛, 谢欣序, 崔亚茹, 等. 中药多糖治疗化疗性骨髓抑制的药理作用研究进展[J]. 中华中医药学刊, 2024, 42(4): 158-164, 275. [Zang JT, Xie XX, Cui YR, et al. Mechanism of traditional Chinese medicine polysaccharides in treatment of chemotherapeutic myelosuppression: a review[J]. Chinese Journal of Traditional Chinese Medicine, 2024, 42(4): 158-164, 275. ] DOI: 10.13193/j.issn.1673-7717.2024.04.031.

53. Sougiannis AT, VanderVeen BN, Davis JM, et al. Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience[J]. Am J Physiol Gastrointest Liver Physiol, 2021, 320(5): G712-G719. DOI: 10.1152/ajpgi.00380.2020.

54. Wang M, Fu R, Xu D, et al. Traditional Chinese medicine: a promising strategy to regulate the imbalance of bacterial flora, impaired intestinal barrier and immune function attributed to ulcerative colitis through intestinal microecology[J]. J Ethnopharmacol, 2024, 318(Pt A): 116879. DOI: 10.1016/j.jep.2023.116879.

55. Chen L, Ji N, Zhang M, et al. The influence of Wuzhi capsule on the pharmacokinetics of cyclophosphamide[J]. Recent Pat Anticancer Drug Discov, 2022, 17(2): 195-203. DOI: 10.2174/15748928166662 11110152119.

56. Duan XY, Fan XY, Jiang HY, et al. Herb-drug interactions in oncology: pharmacodynamic/pharmacokinetic mechanisms and risk prediction[J]. Chin Med, 2025, 20(1): 107. DOI: 10.1186/s13020-025-01156-4.

57. Tang YP, Xu DQ, Yue SJ, et al. Modern research thoughts and methods on bio-active components of TCM formulae[J]. Chin J Nat Med, 2022, 20(7): 481-493. DOI: 10.1016/S1875-5364(22)60206-1.

58. Allegra S, Chiara F, Abbadessa G, et al. Interactions between phytotherapeutics and chemotherapeutics: the current evidence[J]. Expert Opin Drug Metab Toxicol, 2025, 21(7): 831-845. DOI: 10.1080/17425255.2025.2517733.

59. Bi Y, Wang X, Ding H, et al. Transporter-mediated natural product-drug interactions[J]. Planta Med, 2023, 89(2): 119-133. DOI: 10.1055/a-1803-1744.

60. Pomeroy AE, Schmidt EV, Sorger PK, et al. Drug independence and the curability of cancer by combination chemotherapy[J]. Trends Cancer, 2022, 8(11): 915-929. DOI: 10.1016/j.trecan.2022.06.009.

61. Esmeeta A, Adhikary S, Dharshnaa V, et al. Plant-derived bioactive compounds in colon cancer treatment: an updated review[J]. Biomed Pharmacother, 2022, 153: 113384. DOI: 10.1016/j.biopha.2022.113384.

62. Jenča A, Mills DK, Ghasemi H, et al. Herbal therapies for cancer treatment: a review of phytotherapeutic efficacy[J]. Biologics, 2024, 18: 229-255. DOI: 10.2147/BTT.S484068.

63. Li B, Shao H, Gao L, et al. Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review[J]. Drug Deliv, 2022, 29(1): 2130-2161. DOI: 10.1080/10717544.2022.2094498

64. Li M, Wang Y, Chen Y, et al. A comprehensive review on pharmacokinetic mechanism of herb-herb/drug interactions in Chinese herbal formula[J]. Pharmacol Ther, 2024, 264: 108728. DOI: 10.1016/j.pharmthera.2024.108728.

65. Kamal R, Awasthi A, Paul P, et al. Novel drug delivery systems in colorectal cancer: advances and future prospects[J]. Pathol Res Pract, 2024, 262: 155546. DOI: 10.1016/j.prp.2024.155546.

66.