中药干预上皮-间质转化治疗宫颈癌的机制

doi:10.12280/gjszjk.20250382

摘要/Abstract

摘要：

宫颈癌的发展和转移与上皮-间质转化（epithelial-mesenchymal transition，EMT）密切相关，中药在干预EMT引起的宫颈癌转移和侵袭中具有独特的优势。总结近年来中药干预EMT治疗宫颈癌的作用机制，发现中药有效成分可通过磷脂酰肌醇3激酶（phosphoinositide 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）、转化生长因子-β（transforming growth factor-β，TGF-β）、表皮生长因子受体（epidermal growth factor receptor，EGFR）、信号转导及转录活化因子3（signal transducer and activator of transcription 3，STAT3）、Wnt、Notch等信号通路，调控核心的EMT诱导转录因子、上皮细胞标志物和间质细胞标志物表达，阻止上皮细胞向间质表型转变。未来有必要进行进一步的基础研究和临床试验，以期为中药创新药的开发提供参考。

关键词: 宫颈肿瘤, 癌, 上皮-间质转化, 中药, 信号传导, 治疗

Abstract:

The development and metastasis of cervical cancer are closely related to epithelial-mesenchymal transition (EMT), and traditional Chinese medicine has unique advantages in intervening in the metastasis and invasion of cervical cancer caused by EMT. To summarize the mechanism of traditional Chinese medicine intervention in the treatment of cervical cancer in recent years, it was found that the active ingredients of traditional Chinese medicine can regulate the expression of core EMT-induced transcription factors, epithelial cell markers and mesenchymal cell markers through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), transforming growth factor-β (TGF-β), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), Wnt, Notch and other signaling pathways, so as to prevent the transition of epithelial cells to a mesenchymal phenotype. In the future, it is necessary to conduct further basic research and clinical trials to provide more references for the development of innovative traditional Chinese medicine drugs.

Key words: Uterine cervical neoplasms, Carcinoma, Epithelial-mesenchymal transition, Traditional Chinese drugs, Signal transduction, Therapy

高越, 余健楠, 张丽倩, 石百超, 王宇, 吴效科. 中药干预上皮-间质转化治疗宫颈癌的机制[J]. 国际生殖健康/计划生育杂志, 2026, 45(1): 77-82.

GAO Yue, YU Jian-nan, ZHANG Li-qian, SHI Bai-chao, WANG Yu, WU Xiao-ke. Mechanism of Traditional Chinese Medicine in Treatment of Cervical Cancer by the Intervention of Epithelial-Mesenchymal Transition[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(1): 77-82.

参考文献 40

[1]	Cao G, Yue J, Ruan Y, et al. Single-cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment[J]. EMBO J, 2023, 42(16):e110757. doi: 10.15252/embj.2022110757.
[2]	Wei X, Liu R, Li W, et al. Advances in research regarding epithelial-mesenchymal transition and prostate cancer[J]. Front Cell Dev Biol, 2025, 13:1583255. doi: 10.3389/fcell.2025.1583255.
[3]	史宇思, 范乐. 中医药分阶段防治宫颈癌思路初探[J]. 中医杂志, 2025, 66(2):193-196. doi: 10.13288/j.11-2166/r.2025.02.015.
[4]	Ray I, Michael A, Meira LB, et al. The Role of Cytokines in Epithelial-Mesenchymal Transition in Gynaecological Cancers: A Systematic Review[J]. Cells, 2023, 12(3):416. doi: 10.3390/cells12030416.
[5]	Xie Y, Wang X, Wang W, et al. Epithelial-mesenchymal transition orchestrates tumor microenvironment: current perceptions and challenges[J]. J Transl Med, 2025, 23(1):386. doi: 10.1186/s12967-025-06422-5. pmid: 40176117
[6]	Huang Z, Zhang Z, Zhou C, et al. Epithelial-mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities[J]. MedComm(2020), 2022, 3(2):e144. doi: 10.1002/mco2.144.
[7]	Lee J, You JH, Kim MS, et al. Epigenetic reprogramming of epithelial-mesenchymal transition promotes ferroptosis of head and neck cancer[J]. Redox Biol, 2020, 37:101697. doi: 10.1016/j.redox.2020.101697.
[8]	Huang Y, Hong W, Wei X. The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis[J]. J Hematol Oncol, 2022, 15(1):129. doi: 10.1186/s13045-022-01347-8.
[9]	Su H, Peng C, Liu Y. Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer[J]. Front Cell Dev Biol, 2024, 12:1372330. doi: 10.3389/fcell.2024.1372330.
[10]	Maharati A, Moghbeli M. PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells[J]. Cell Commun Signal, 2023, 21(1):201. doi: 10.1186/s12964-023-01225-x. pmid: 37580737
[11]	Lu J, Liu Q, Zhu L, et al. Endothelial cell-specific molecule 1 drives cervical cancer progression[J]. Cell Death Dis, 2022, 13(12):1043. doi: 10.1038/s41419-022-05501-5. pmid: 36522312
[12]	Mohan CD, Rangappa S, Preetham HD, et al. Targeting STAT3 signaling pathway in cancer by agents derived from Mother Nature[J]. Semin Cancer Biol, 2022, 80:157-182. doi: 10.1016/j.semcancer.2020.03.016.
[13]	Adesoye T, Tripathy D, Hunt KK, et al. Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics[J]. Cancers(Basel), 2024, 16(3):492. doi: 10.3390/cancers16030492.
[14]	Zhao Z, Yu P, Wang Y, et al. Silencing of STEAP3 suppresses cervical cancer cell proliferation and migration via JAK/STAT3 signaling pathway[J]. Cancer Metab, 2024, 12(1):40. doi: 10.1186/s40170-024-00370-2. pmid: 39736751
[15]	Sui HY, Cui XY, Shi CX, et al. LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression[J]. Cancer Sci, 2023, 114(6):2634-2649. doi: 10.1111/cas.15780.
[16]	Yang J, Sun Q, Liu X, et al. Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer[J]. Front Pharmacol, 2024, 15:1412669. doi: 10.3389/fphar.2024.1412669.
[17]	Shi Q, Xue C, Zeng Y, et al. Notch signaling pathway in cancer: from mechanistic insights to targeted therapies[J]. Signal Transduct Target Ther, 2024, 9(1):128. doi: 10.1038/s41392-024-01828-x.
[18]	Sun T, Zhang D, Wang Z, et al. Inhibition of the notch signaling pathway overcomes resistance of cervical cancer cells to paclitaxel through retardation of the epithelial-mesenchymal transition process[J]. Environ Toxicol, 2021, 36(9):1758-1764. doi: 10.1002/tox.23296.
[19]	Zhang Y. Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor[J]. Pharmacol Rev, 2023, 75(6):1218-1232. doi: 10.1124/pharmrev.123.000906. pmid: 37339882
[20]	Morgan EL, Scarth JA, Patterson MR, et al. E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer[J]. Cell Death Differ, 2021, 28(5):1669-1687. doi: 10.1038/s41418-020-00693-9.
[21]	Deng Z, Fan T, Xiao C, et al. TGF-β signaling in health, disease, and therapeutics[J]. Signal Transduct Target Ther, 2024, 9(1):61. doi: 10.1038/s41392-024-01764-w.
[22]	Lei ZN, Teng QX, Koya J, et al. The correlation between cancer stem cells and epithelial-mesenchymal transition: molecular mechanisms and significance in cancer theragnosis[J]. Front Immunol, 2024, 15:1417201. doi: 10.3389/fimmu.2024.1417201.
[23]	Zhu X, Chen L, Liu L, et al. EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies[J]. Front Oncol, 2019, 9:1044. doi: 10.3389/fonc.2019.01044. pmid: 31681582
[24]	Zhong G, Zhao Q, Chen Z, et al. TGF-β signaling promotes cervical cancer metastasis via CDR1as[J]. Mol Cancer, 2023, 22(1):66. doi: 10.1186/s12943-023-01743-9. pmid: 37004067
[25]	Wu X, Que H, Li Q, et al. Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy[J]. Mol Cancer, 2025, 24(1):171. doi: 10.1186/s12943-025-02363-1. pmid: 40495229
[26]	Xue W, Yang L, Chen C, et al. Wnt/β-catenin-driven EMT regulation in human cancers[J]. Cell Mol Life Sci, 2024, 81(1):79. doi: 10.1007/s00018-023-05099-7. pmid: 38334836
[27]	Cheng Z, Wang H, Yang Z, et al. LMP2 and TAP2 impair tumor growth and metastasis by inhibiting Wnt/β-catenin signaling pathway and EMT in cervical cancer[J]. BMC Cancer, 2023, 23(1):1128. doi: 10.1186/s12885-023-11639-y. pmid: 37986152
[28]	Chen YH, Wu JX, Yang SF, et al. Anticancer Effects and Molecular Mechanisms of Apigenin in Cervical Cancer Cells[J]. Cancers(Basel), 2022, 14(7):1824. doi: 10.3390/cancers14071824.
[29]	Chen Y, Chen S, Chen K, et al. Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways[J]. Chin Herb Med, 2024, 16(1):94-105. doi: 10.1016/j.chmed.2023.01.004. pmid: 38375055
[30]	Nayim P, Mbaveng AT, Sanjukta M, et al. CD24 gene inhibition and TIMP-4 gene upregulation by Imperata cylindrica's root extract prevents metastasis of CaSki cells via inhibiting PI3K/Akt/snail signaling pathway and blocking EMT[J]. J Ethnopharmacol, 2021, 275:114111. doi: 10.1016/j.jep.2021.114111.
[31]	曲长萍, 田君, 霍会蚕, 等. 黄芩素通过miR-410/JAK2/STAT3轴对宫颈癌SiHa细胞增殖、侵袭及上皮间质转化的影响[J]. 实用医学杂志, 2022, 38(10):1208-1212. doi: 10.3969/j.issn.1006-5725.2022.10.007.
[32]	胡艳玲, 李国利, 石中全, 等. 异土木香内酯对宫颈癌细胞迁移、侵袭和上皮间质转化的影响[J]. 中国临床药理学杂志, 2022, 38(8):787-790,806. doi: 10.13699/j.cnki.1001-6821.2022.08.008.
[33]	刘丽, 魏孝东, 夏铭遥. β-榄香烯调节Notch1/Hes1信号通路对宫颈癌细胞增殖、凋亡和放射敏感性的影响[J]. 中国优生与遗传杂志, 2023, 31(8):1565-1570. doi: 10.13404/j.cnki.cjbhh.2023.08.007.
[34]	刘佳, 严金金, 纪贤芬. 麦冬皂苷B调节Notch/Snail信号通路对宫颈癌细胞迁移、侵袭和上皮间质转化的影响[J]. 解剖学杂志, 2024, 47(6):500-505. doi: 10.3969/j.issn.1001-1633.2024.06.007.
[35]	江晓聪, 潘秀花, 蔡文娟, 等. 和厚朴酚对宫颈癌细胞血管生成拟态及上皮间质转化的影响[J]. 世界临床药物, 2023, 44(9):922-932. doi: 10.13683/j.wph.2023.09.006.
[36]	Krishnamoorthy S, Sabanayagam R, Periyasamy L, et al. Plumbagin as a preferential lead molecule to combat EGFR-driven matrix abundance and migration of cervical carcinoma cells[J]. Med Oncol, 2024, 41(4):89. doi: 10.1007/s12032-024-02332-6. pmid: 38520625
[37]	张蕾, 黄华明, 周杰, 等. 原花青素对宫颈癌HeLa细胞上皮间质转化的抑制作用[J]. 中成药, 2021, 43(7):1733-1740. doi: 10.3969/j.issn.1001-1528.2021.07.010.
[38]	Shen L, Li Y, Hu G, et al. Astragaloside IV suppresses the migration and EMT progression of cervical cancer cells by inhibiting macrophage M2 polarization through TGFβ/Smad2/3 signaling[J]. Funct Integr Genomics, 2023, 23(2):133. doi: 10.1007/s10142-023-01017-z.
[39]	任璐, 曹芹雪, 杨少琴. 紫花前胡苷调控EMT对宫颈癌细胞侵袭迁移的影响及其作用机制[J]. 解放军医学杂志, 2022, 47(5):451-457. doi: 10.11855/j.issn.0577-7402.2022.05.0451.
[40]	Chai Y, Yu S, Lin G, et al. Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway[J]. Int J Mol Sci, 2025, 26(10):4630. doi: 10.3390/ijms26104630.