Research progress on the role of Warburg effect in ulcerative colitis-carcinoma transformation and intervention of traditional Chinese medicine
-
摘要: 在溃疡性结肠炎(ulcerative colitis，UC)患者进化为结直肠癌(colorectal cancer，CRC)的过程中，炎-癌转化的机制仍不明确，本文重点分析了瓦博格效应在其中的作用以及中医药干预的潜力和研究进展。UC作为一种慢性炎症性肠道疾病，其长期存在可能导致结肠黏膜发生异型增生，最终进展为CRC。在长期慢性炎症状态下，细胞发生的代谢重编程会导致细胞形成瓦博格效应，这一效应可通过增强氧化应激、形成肿瘤微环境、助推炎症及癌症细胞的增殖与转化而推动炎-癌转化。中药单味提取物与复方可对这一过程进行干预，具有重要的临床应用前景和研究价值。尽管结肠炎相关癌症发病机制的研究已有一定规模，但从能量代谢角度出发，对UC转化为CRC的机制进行的研究仍然较少，且多为网络药理学、动物试验等，缺乏真实可靠的临床数据。此外，中药复方干预能量代谢的研究数量不足，今后应将中药辨证论治与能量代谢相结合，实现对炎-癌转化的中药复方干预。Abstract: During the process in which patients with ulcerative colitis progress to colorectal cancer, the mechanism of the transformation from inflammation to cancer remains unclear. This article mainly analyzes the role of the Warburg effect in this process, as well as the potential and research progress of traditional Chinese medicine intervention. Ulcerative colitis(UC), as a chronic inflammatory bowel disease, may lead to dysplasia of the colonic mucosa in the long term and eventually progress to colorectal cancer(CRC). Under the condition of long-term chronic inflammation, metabolic reprogramming occurs in cells, giving rise to the Warburg effect. This effect can promote the transformation from inflammation to cancer by means of oxidative stress, the formation of the tumor microenvironment, and facilitating cell proliferation and transformation. Single-herb extracts and compound prescriptions of traditional Chinese medicine can intervene in this process and possess significant prospects for clinical application and research value. Although research on the pathogenesis of colitis-associated cancer has reached a certain scale, studies on the mechanism of the transformation from UC to CRC from the perspective of energy metabolism are still relatively few. Moreover, most of these studies are based on network pharmacology, animal experiments, etc., lacking authentic and reliable clinical data. In addition, the number of studies on the intervention of traditional Chinese medicine compound prescriptions in energy metabolism is insufficient. In the future, the syndrome differentiation and treatment of traditional Chinese medicine should be combined with energy metabolism to achieve precise intervention in the transformation from inflammation to cancer.
-
-
[1] Abedizadeh R, Majidi F, Khorasani HR, et al. Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments[J]. Cancer Metastasis Rev, 2024, 43(2): 729-753. doi: 10.1007/s10555-023-10158-3
[2] Zhao Y, Zhou R, Xie BQ, et al. Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients[J]. Nat Commun, 2025, 16(1): 904. doi: 10.1038/s41467-025-56212-2
[3] Qu HD, Liu JL, Zhang D, et al. Glycolysis in chronic liver diseases: mechanistic insights and therapeutic opportunities[J]. Cells, 2023, 12(15): 1930. doi: 10.3390/cells12151930
[4] 赵珠琳. 溃疡性结肠炎向结肠癌转化关键基因的筛选及中药预测研究[D]. 沈阳: 中国医科大学, 2023.
[5] 智慧, 龙健, 刘可云. 溃疡性结肠炎中西医治疗研究进展[J]. 现代医药卫生, 2023, 39(8): 1366-1369, 1374.
[6] Wei XN, Leng XH, Li GY, et al. Advances in research on the effectiveness and mechanism of Traditional Chinese Medicine formulas for colitis-associated colorectal cancer[J]. Front Pharmacol, 2023, 14: 1120672. doi: 10.3389/fphar.2023.1120672
[7] 中国中西医结合学会. 溃疡性结肠炎中西医结合诊疗专家共识[J]. 中国中西医结合杂志, 2023, 43(1): 5-11.
[8] 刘一帆, 王成志, 席作武, 等. 结肠炎癌转化调控机制以及中药活性成分干预的研究进展[J]. 世界中医药, 2024, 19(20): 3174-3180.
[9] Wang YS, Wang P, Shao LX. Correlation of ulcerative colitis and colorectal cancer: a systematic review and meta-analysis[J]. J Gastrointest Oncol, 2021, 12(6): 2814-2822. doi: 10.21037/jgo-21-624
[10] 鲍淑梅, 张亚杰, 田丰. 炎症性肠病合并结直肠癌的流行病学和防治进展[J]. 中国临床医生杂志, 2021, 49(12): 1409-1413.
[11] Liu J, Li SM, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients[J]. EBioMedicine, 2020, 55: 102763. doi: 10.1016/j.ebiom.2020.102763
[12] Tong G, Shen Y, Li H, et al. NLRC4, inflammation and colorectal cancer(Review)[J]. Int J Oncol, 2024, 65(4): 99. doi: 10.3892/ijo.2024.5687
[13] 刘佳丽, 孙平良, 肖团有, 等. miRNA调控NF-κB通路干预溃疡性结肠炎相关癌变及中医药作用研究进展[J]. 世界科学技术-中医药现代化, 2022, 24(5): 1895-1901.
[14] 杜俊娥, 曹琰. 溃疡性结肠炎相关性结直肠癌的危险因素研究[J]. 贵州医药, 2024, 48(12): 1921-1923.
[15] Jaworska M, Szczudł OJ, Pietrzyk A, et al. The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells[J]. Pharmacol Rep, 2023, 75(4): 876-890. doi: 10.1007/s43440-023-00504-1
[16] Fukushi A, Kim HD, Chang YC, et al. Revisited metabolic control and reprogramming cancers by means of the Warburg effect in tumor cells[J]. Int J Mol Sci, 2022, 23(17): 10037. doi: 10.3390/ijms231710037
[17] Zahra K, Dey T, Ashish, et al. Pyruvate kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis[J]. Front Oncol, 2020, 10: 159. doi: 10.3389/fonc.2020.00159
[18] Bie JT, Li RD, Li YT, et al. PKM2 aggregation drives metabolism reprograming during aging process[J]. Nat Commun, 2024, 15(1): 5761. doi: 10.1038/s41467-024-50242-y
[19] Shi B, Chen JJ, Guo HR, et al. ACOX1 activates autophagy via the ROS/mTOR pathway to suppress proliferation and migration of colorectal cancer[J]. Sci Rep, 2025, 15(1): 2992. doi: 10.1038/s41598-025-87728-8
[20] Li YJ, Zhang CY, Martincuks A, et al. STAT proteins in cancer: orchestration of metabolism[J]. Nat Rev Cancer, 2023, 23(3): 115-134. doi: 10.1038/s41568-022-00537-3
[21] Sharifi-Rad M, Anil Kumar NV, Zucca P, et al. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases[J]. Front Physiol, 2020, 11: 694. doi: 10.3389/fphys.2020.00694
[22] Hao JC, Liu C, Gu ZJ, et al. Dysregulation of Wnt/β-catenin signaling contributes to intestinal inflammation through regulation of group 3 innate lymphoid cells[J]. Nat Commun, 2024, 15(1): 2820. doi: 10.1038/s41467-024-45616-1
[23] Zhao Y, Shen ML, Wu LQ, et al. Stromal cells in the tumor microenvironment: accomplices of tumor progression?[J]. Cell Death Dis, 2023, 14(9): 587. doi: 10.1038/s41419-023-06110-6
[24] Yang XG, Lu Y, Hang JJ, et al. Lactate-modulated immunosuppression of myeloid-derived suppressor cells contributes to the radioresistance of pancreatic cancer[J]. Cancer Immunol Res, 2020, 8(11): 1440-1451. doi: 10.1158/2326-6066.CIR-20-0111
[25] Yang K, Xu JJ, Fan M, et al. Lactate suppresses macrophage pro-inflammatory response to LPS stimulation by inhibition of YAP and NF-κB activation via GPR81-mediated signaling[J]. Front Immunol, 2020, 11: 587913. doi: 10.3389/fimmu.2020.587913
[26] Xiong J, He J, Zhu J, et al. Lactylation-driven METTL3-mediated RNA m(6) a modification promotes immunosuppression of tumor-infiltrating myeloid cells[J]. Mol Cell, 2022, 82(9): 1660-1677. e10. doi: 10.1016/j.molcel.2022.02.033
[27] Qiu YJ, Su YP, Xie EM, et al. Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity[J]. Cancer Cell, 2025, 43(1): 103-121. e8. doi: 10.1016/j.ccell.2024.11.003
[28] 蒋世芳, 曹立军, 贺学强, 等. 美沙拉秦联合昂丹司琼对溃疡性结肠炎患者肠黏膜屏障功能及炎症因子水平的影响[J]. 中国医药, 2023, 18(8): 1211-1215.
[29] Zhang C, Chen HL, He QL, et al. Fibrinogen/AKT/microfilament axis promotes colitis by enhancing vascular permeability[J]. Cell Mol Gastroenterol Hepatol, 2021, 11(3): 683-696. doi: 10.1016/j.jcmgh.2020.10.007
[30] 葛鹏志, 李经纬, 赵海梅, 等. 基于文献计量学及可视化技术的中医药治疗溃疡性结肠炎研究现状及热点分析[J]. 中医临床研究, 2024, 16(16): 136-143.
[31] Wang XL, Hu Y, Li XR, et al. Mycoplasma genitaliummembrane lipoprotein induces GAPDH malonylation in urethral epithelial cells to regulate cytokine response[J]. Microb Pathog, 2024, 195: 106872. doi: 10.1016/j.micpath.2024.106872
[32] Yang M, Chen QS, Mei L, et al. Neutrophil elastase promotes neointimal hyperplasia by targeting toll-like receptor 4(TLR4)-NF-κB signalling[J]. Br J Pharmacol, 2021, 178(20): 4048-4068. doi: 10.1111/bph.15583
[33] Tang J, Chen L, Qin ZH, et al. Structure, regulation, and biological functions of TIGAR and its role in diseases[J]. Acta Pharmacol Sin, 2021, 42(10): 1547-1555. doi: 10.1038/s41401-020-00588-y
[34] Tan LL, Jiang XL, Xu LX, et al. TP53-induced glycolysis and apoptosis regulator alleviates hypoxia/ischemia-induced microglial pyroptosis and ischemic brain damage[J]. Neural Regen Res, 2021, 16(6): 1037-1043. doi: 10.4103/1673-5374.300453
[35] Liu YQ, Su ZY, Tavana O, et al. Understanding the complexity of p53 in a new era of tumor suppression[J]. Cancer Cell, 2024, 42(6): 946-967. doi: 10.1016/j.ccell.2024.04.009
[36] Mazurakova A, Koklesova L, Csizmár SH, et al. Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells-A potential contribution to the predictive, preventive, and personalized medicine[J]. J Adv Res, 2024, 55: 103-118. doi: 10.1016/j.jare.2023.02.015
[37] Wang JZ, Yang PL, Yu TY, et al. Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages[J]. Int J Biol Sci, 2022, 18(16): 6210-6225. doi: 10.7150/ijbs.75434
[38] Shi JY, Ji XD, Shan SH, et al. The interaction between apigenin and PKM2 restrains progression of colorectal cancer[J]. J Nutr Biochem, 2023, 121: 109430. doi: 10.1016/j.jnutbio.2023.109430
[39] Chen JR, Zhong KX, Jing YQ, et al. Procyanidin B2: a promising multi-functional food-derived pigment for human diseases[J]. Food Chem, 2023, 420: 136101. doi: 10.1016/j.foodchem.2023.136101
[40] Xue PY, Zhao HM, You XY, et al. Structural and in vitro anticancer properties of the kaempferol-lactoferrin complex[J]. Food Sci Nutr, 2024, 12(11): 9046-9055. doi: 10.1002/fsn3.4479
[41] 阿地力江·萨吾提, 木塔力甫·艾买提, 周文婷, 等. 山柰酚诱导人乳腺癌耐阿霉素细胞MCF-7/阿霉素凋亡的研究[J]. 中国临床药理学杂志, 2021, 37(11): 1380-1384.
[42] Sood A, Mehrotra A, Sharma U, et al. Advancements and recent explorations of anti-cancer activity of chrysin: from molecular targets to therapeutic perspective[J]. Explor Target Antitumor Ther, 2024, 5(3): 477-494. doi: 10.37349/etat.2024.00230
[43] Li J, Zou YL, Pei ML, et al. Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells[J]. J Cancer, 2021, 12(1): 207-216. doi: 10.7150/jca.48896
[44] Song CH, Li HW, Huang ZC, et al. Matrine inhibits cell proliferation, invasion, and stem cell formation in hepatocellular carcinoma by regulating the ELAVL1/RBM3-mediated Wnt/β-catenin signaling pathway[J]. Chem Biol Drug Des, 2024, 103(2): e14442. doi: 10.1111/cbdd.14442
[45] Ji LJ, Shen WX, Zhang F, et al. Worenine reverses the Warburg effect and inhibits colon cancer cell growth by negatively regulating HIF-1α[J]. Cell Mol Biol Lett, 2021, 26(1): 19. doi: 10.1186/s11658-021-00263-y
[46] Liu WB, Yu XF, Zhou L, et al. Sinomenine inhibits non-small cell lung cancer via downregulation of hexokinases Ⅱ-mediated aerobic glycolysis[J]. Onco Targets Ther, 2020, 13: 3209-3221. doi: 10.2147/OTT.S243212
[47] 范春娇, 黄鹏, 黄贵华, 等. 吴茱萸碱抗消化系统肿瘤作用机制的研究进展[J]. 海南医学院学报, 2021, 27(10): 791-796.
[48] Li M, Gao F, Zhao Q, et al. Tanshinone ⅡA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis[J]. Cell Death Dis, 2020, 11(5): 381. doi: 10.1038/s41419-020-2579-9
[49] Jin Z, Yun L, Cheng P. TanshinoneⅠ reprograms glycolysis metabolism to regulate histone H3 lysine 18 lactylation(H3K18la)and inhibits cancer cell growth in ovarian cancer[J]. Int J Biol Macromol, 2024, 291: 139072.
[50] Hu XX, Peng XY, Zhang Y, et al. Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect[J]. Phytomedicine, 2024, 123: 155214. doi: 10.1016/j.phymed.2023.155214
[51] Ahmad H, Crotts MS, Jacobs JC, et al. Shikonin causes non-apoptotic cell death in B16F10 melanoma[J]. Anticancer Agents Med Chem, 2023, 23(16): 1880-1887. doi: 10.2174/1871520623666230701000338
[52] Yang C, Yang L, Li DH, et al. Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis[J]. Heliyon, 2024, 10(14): e34291. doi: 10.1016/j.heliyon.2024.e34291
[53] 梁晓晖, 石海莲, 吴晓俊. 糖代谢重编程与"炎-癌转化"及抗炎中药靶向肿瘤糖代谢抗肿瘤作用机制研究进展[J]. 中国药理学与毒理学杂志, 2021, 35(11): 859-867.
[54] 骆李康, 王译峰, 陈云洋, 等. 双氢青蒿素抗消化道恶性肿瘤作用及机制研究进展[J]. 现代肿瘤医学, 2024, 32(4): 737-743. doi: 10.3969/j.issn.1672-4992.2024.04.027
[55] Ding ZJ, Xi JM, Zhong M, et al. Cynaropicrin induces cell cycle arrest and apoptosis by inhibiting PKM2 to cause DNA damage and mitochondrial fission in A549 cells[J]. J Agric Food Chem, 2021, 69(45): 13557-13567. doi: 10.1021/acs.jafc.1c05394
[56] 袁彬, 韦燕飞, 周凤玲, 等. 齐墩果酸抗肿瘤作用及机制研究进展[J]. 中国医药导报, 2023, 20(33): 60-62, 66.
[57] Verma N, Raghuvanshi DS, Singh RV. Recent advances in the chemistry and biology of oleanolic acid and its derivatives[J]. Eur J Med Chem, 2024, 276: 116619.
[58] Huang R, Zhang LJ, Jin JM, et al. Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction[J]. Acta Pharm Sin B, 2021, 11(11): 3481-3492.
[59] 董立强. 雷公藤红素与汉黄芩素联合应用对肿瘤细胞能量代谢的影响[D]. 哈尔滨: 哈尔滨商业大学, 2016.
[60] 孙梦瑶, 王丹丹, 吴秋雪, 等. 左金丸对胃癌耐药细胞SGC-7901/DDP增殖和糖酵解的抑制作用[J]. 上海中医药大学学报, 2019, 33(1): 71-75.
[61] 严卿莹, 阮善明, 张恺, 等. 解毒三根汤调控糖酵解逆转人结肠癌LOVO/5-FU细胞株耐药的机制[J]. 中华中医药杂志, 2019, 34(4): 1751-1756.
[62] 夏孟蛟, 由凤鸣, 郑川, 等. 论风药治肿瘤[J]. 中医杂志, 2017, 58(2): 115-118.
[63] 林才志, 胡乃强, 赵海燕, 等. 论风药在溃疡性结肠炎中治疗的应用[J]. 辽宁中医杂志, 2018, 45(5): 954-957.
[64] 蒋义芳. 补中益气汤调控能量代谢重编程干预结肠炎癌转化的效应与机制研究[D]. 成都: 成都中医药大学, 2019.
[65] Liu MH, Wang ZH, Liu X, et al. Therapeutic effect of Yiyi Fuzi Baijiang formula on TNBS-induced ulcerative colitis via metabolism and Th17/Treg cell balance[J]. J Ethnopharmacol, 2023, 309: 116301.
[66] 刘怡辰, 诸君, 张国磊, 等. 益气扶正方通过调控肿瘤相关巨噬细胞极化抗肺癌转移的实验研究[J]. 上海中医药杂志, 2022, 56(2): 67-74.
[67] 李沐涵, 李景南. 溃疡性结肠炎癌变相关机制研究进展[J]. 中国中西医结合消化杂志, 2023, 31(4): 243-249. https://zxyxh.whuhzzs.com/article/doi/10.3969/j.issn.1671-038X.2023.04.02
[68] 曾铖, 顾思臻, 黄诗韵, 等. 基于信号通路探讨清热方药调控溃疡性结肠炎"炎癌转化"的研究进展[J]. 中国中西医结合消化杂志, 2024, 32(2): 170-175. https://zxyxh.whuhzzs.com/article/doi/10.3969/j.issn.1671-038X.2024.02.16
-
计量
- 文章访问数: 187
- 施引文献: 0
下载: