切换至 "中华医学电子期刊资源库"

中华乳腺病杂志(电子版) ›› 2026, Vol. 20 ›› Issue (01) : 55 -59. doi: 10.3877/cma.j.issn.1674-0807.2026.01.008

综述

雷公藤提取物在三阴性乳腺癌中的作用机制
赵珂欣1, 王蓉1, 张钧1, 杨哲1, 石钰环1, 姬雅楠1, 刘敏丽1, 张生军1,2,()   
  1. 1 716000 延安,延安大学延安医学院第一临床医学系
    2 716000 延安,延安大学附属医院甲状腺乳腺外科
  • 收稿日期:2025-06-24 出版日期:2026-02-01
  • 通信作者: 张生军
  • 基金资助:
    吴阶平医学基金会科研专项资助基金项目(320.6750.2024-21-104)

Application of tripterygium wilfordii extract in the treatment of triple negative breast cancer

Kexin Zhao, Rong Wang, Jun Zhang, Zhe Yang   

  • Received:2025-06-24 Published:2026-02-01
引用本文:

赵珂欣, 王蓉, 张钧, 杨哲, 石钰环, 姬雅楠, 刘敏丽, 张生军. 雷公藤提取物在三阴性乳腺癌中的作用机制[J/OL]. 中华乳腺病杂志(电子版), 2026, 20(01): 55-59.

Kexin Zhao, Rong Wang, Jun Zhang, Zhe Yang. Application of tripterygium wilfordii extract in the treatment of triple negative breast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2026, 20(01): 55-59.

三阴性乳腺癌(TNBC)是乳腺癌中最具侵袭性的分子亚型,与早期复发和远处转移的高发生率、治疗耐药的频繁发生以及不良预后相关。由于TNBC缺乏ER、PR及HER-2的表达,目前尚无靶向治疗被批准用于治疗TNBC,常规化疗仍是临床主要的治疗选择,但大多数TNBC患者会对化疗产生耐药性,从而导致不良的临床结果。近年来,传统中草药雷公藤及其提取物由于可下调XRCC1、PARP1、NF-κB、CDK1/4、Twist1、Notch1等多种肿瘤干细胞相关基因表达的能力,在治疗TNBC方面受到了广泛关注。本文总结了从传统中草药雷公藤中提取的天然化合物对TNBC的抗癌作用及相关机制。雷公藤提取物能够通过不同的途径抑制体外人TNBC细胞生长和TNBC异种移植乳腺肿瘤的生长,有望成为治疗TNBC的新型药物。

[1]
Sung HFerlay JSiegel RL,et al. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin202171(3): 209-249.
[2]
Jiang YZMa DSuo C,et al. Genomic and transcriptomic landscape of triple-negative breast cancers:subtypes and treatment strategies [J]. Cancer Cell201935(3):428-440. e5.
[3]
Medina MAOza GSharma A,et al. Triple-negative breast cancer: a review of conventional and advanced therapeutic strategies [J]. Int J Environ Res Public Health202017(6):2078.
[4]
Siegel RLMiller KDFuchs HE,et al. Cancer statistics,2021 [J]. CA Cancer J Clin202171(1): 7-33.
[5]
Liao YGui YLi Q,et al. The signaling pathways and targets of natural products from traditional Chinese medicine treating gastric cancer provide new candidate therapeutic strategies [J]. Biochim Biophys Acta Rev Cancer20231878(6):188998.
[6]
Xiu LJSun DZJiao JP,et al. Anticancer effects of traditional Chinese herbs with phlegm-eliminating properties-an overview [J]. J Ethnopharmacol2015172:155-161.
[7]
Lee YWChen TLShih YR,et al. Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer:a population-based study [J]. Cancer2014120(9):1338-1344.
[8]
Ateba SBMvondo MANgeu ST,et al. Natural terpenoids against female breast cancer:a 5-year recent research [J]. Curr Med Chem201825(27):3162-3213.
[9]
Liu ZMa LZhou GB. The main anticancer bullets of the Chinese medicinal herb,thunder god vine [J]. Molecules201116(6):5283-5297.
[10]
Kupchan SMCourt WADailey RG Jr,et al. Triptolide and tripdiolide,novel antileukemic diterpenoid triepoxides from tripterygium wilfordii [J]. J Am Chem Soc197294(20):7194-7195.
[11]
Li XJJiang ZZZhang LY. Triptolide:progress on research in pharmacodynamics and toxicology [J]. J Ethnopharmacol2014155(1):67-79.
[12]
Wang CDai SZhao X,et al. Celastrol as an emerging anticancer agent:current status,challenges and therapeutic strategies [J]. Biomed Pharmacother2023163:114882.
[13]
Jang SYJang SWKo J. Celastrol inhibits the growth of estrogen positive human breast cancer cells through modulation of estrogen receptor α [J]. Cancer Lett2011300(1):57-65.
[14]
Yang BZhang BCao Z,et al. The lipogenic LXR-SREBF1 signaling pathway controls cancer cell DNA repair and apoptosis and is a vulnerable point of malignant tumors for cancer therapy [J]. Cell Death Differ202027(8):2433-2450.
[15]
Gao BChen JHan B,et al. Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment [J]. Sci Rep202111(1):2408.
[16]
郭少贤,李亚杰,吕博杰,等. 雷公藤联合吉西他滨治疗中晚期胰腺癌的临床效果及安全性分析 [J]. 中国中西医结合消化杂志202028(02):99-103.
[17]
Thompson DEaston DF. Cancer incidence in BRCA1 mutation carriers [J]. J Natl Cancer Inst200294(18):1358-1365.
[18]
Kiwerska KSzyfter K. DNA repair in cancer initiation,progression,and therapy-a double-edged sword [J]. J Appl Genet201960(3/4):329-334.
[19]
London RE. The structural basis of XRCC1-mediated DNA repair [J]. DNA Repair (Amst)201530:90-103.
[20]
Rouleau MPatel AHendzel MJ,et al. PARP inhibition:PARP1 and beyond [J]. Nat Rev Cancer201010(4):293-301.
[21]
Gibson BAKraus WL. New insights into the molecular and cellular functions of poly (ADP-ribose) and PARPs [J]. Nat Rev Mol Cell Biol201213(7):411-424.
[22]
Sarasin AKauffmann A. Overexpression of DNA repair genes is associated with metastasis:a new hypothesis [J]. Mutat Res2008659(1-2):49-55.
[23]
Kou YKoag MCLee S. Structural and kinetic studies of the effect of guanine N7 alkylation and metal cofactors on DNA replication [J]. Biochemistry201857(34):5105-5116.
[24]
Kothandapani ASawant ADangeti VS,et al. Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity [J]. Nucleic Acids Res201341(15):7332-7343.
[25]
Zhang ZSun CZhang L,et al. Triptolide interferes with XRCC1/PARP1-mediated DNA repair and confers sensitization of triple-negative breast cancer cells to cisplatin [J]. Biomed Pharmacother2019109:1541-1546.
[26]
Taher MYDavies DMMaher J. The role of the interleukin (IL)-6/IL-6 receptor axis in cancer [J]. Biochem Soc Trans201846(6):1449-1462.
[27]
Jayatilaka HTyle PChen JJ,et al. Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration [J]. Nat Commun20178:15584.
[28]
Knüpfer HPreiss R. Significance of interleukin-6 (IL-6) in breast cancer (review) [J]. Breast Cancer Res Treat2007102(2):129-135.
[29]
Fu SLin J. Blocking interleukin-6 and interleukin-8 signaling inhibits cell viability,colony-forming activity,and cell migration in human triple-negative breast cancer and pancreatic cancer cells [J]. Anticancer Res201838(11):6271-6279.
[30]
Giridharan SSrinivasan M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation [J]. J Inflamm Res201811:407-419.
[31]
Mulero MCHuxford TGhosh G. NF-κB,IκB,and IKK:integral components of immune system signaling [J]. Adv Exp Med Biol20191172:207-226.
[32]
Okamoto MMizukami Y. Gper negatively regulates TNFα-induced IL-6 production in human breast cancer cells via NF-κB pathway [J]. Endocr J201663(5):485-493.
[33]
Liang SChen ZJiang G,et al. Activation of gper suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-κB/IL-6 signals [J]. Cancer Lett2017386:12-23.
[34]
Yan FWu ZLi Z,et al. Celastrol inhibits migration and invasion of triple-negative breast cancer cells by suppressing interleukin-6 via downregulating nuclear factor-κB (NF-κB) [J]. Med Sci Monit202026:e922814.
[35]
Pines JHunter T. Isolation of a human cyclin cDNA:evidence for cyclin mrna and protein regulation in the cell cycle and for interaction with p34cdc2 [J]. Cell198958(5):833-846.
[36]
Fung TKPoon RY. A roller coaster ride with the mitotic cyclins [J]. Semin Cell Dev Biol200516(3):335-342.
[37]
Peters JM. The anaphase promoting complex/cyclosome:a machine designed to destroy [J]. Nat Rev Mol Cell Biol20067(9):644-656.
[38]
冯立文,虞飞,李姝,等. P53、p21waf-1和cdk1在乳腺癌组织中的表达及意义 [J]. 诊断病理学杂志201926(8):516-518.
[39]
Matsushime HRoussel MFAshmun RA,et al. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle [J]. Cell199165(4):701-713.
[40]
Spring LMWander SAZangardi M,et al. CDK 4/6 inhibitors in breast cancer:current controversies and future directions [J]. Curr Oncol Rep201921(3):25.
[41]
Peng BXu LCao F,et al. HSP90 inhibitor,celastrol,arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way [J]. Mol Cancer20109:79.
[42]
Mishra SJKhandelwal ABanerjee M,et al. Selective inhibition of the Hsp90α isoform [J]. Angew Chem Int Ed Engl202160(19):10547-10551.
[43]
Lee AS. Glucose-regulated proteins in cancer:molecular mechanisms and therapeutic potential [J]. Nat Rev Cancer201414(4):263-276.
[44]
Rozpedek WPytel DMucha B,et al. The role of the PERK/eIF2α/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress [J]. Curr Mol Med201616(6):533-544.
[45]
Patel PDYan PSeidler PM,et al. Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2 [J]. Nat Chem Biol20139(11):677-684.
[46]
Li XSun LHou J,et al. Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer [J]. Int J Cancer2015137(3):512-524.
[47]
Hodorova IRybarova SSolar P,et al. Gp96 and its different expression in breast carcinomas [J]. Neoplasma200855(1):31-35.
[48]
Smid MWang YZhang Y,et al. Subtypes of breast cancer show preferential site of relapse [J]. Cancer Res200868(9):3108-3114.
[49]
Duan XIwanowycz SNgoi S,et al. Molecular chaperone GRP94/GP96 in cancers:oncogenesis and therapeutic target [J]. Front Oncol202111:629846.
[50]
Békés MLangley DRCrews CM. Protac targeted protein degraders:the past is prologue [J]. Nat Rev Drug Discov202221(3):181-200.
[51]
Gan XWang FLuo J,et al. Proteolysis targeting chimeras (protacs) based on celastrol induce multiple protein degradation for triple-negative breast cancer treatment [J]. Eur J Pharm Sci2024192:106624.
[52]
Qu JLi JZhang Y,et al. AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway [J]. Cell Biosci202111(1):163.
[53]
Lee KLChen GChen TY,et al. Effects of cancer stem cells in triple-negative breast cancer and brain metastasis:challenges and solutions [J]. Cancers (Basel)202012(8).
[54]
Zhang DSun BZhao X,et al. Twist1 accelerates tumour vasculogenic mimicry by inhibiting claudin15 expression in triple-negative breast cancer [J]. J Cell Mol Med202024(13):7163-7174.
[55]
Deepak KGKVempati RNagaraju GP,et al. Tumor microenvironment:challenges and opportunities in targeting metastasis of triple negative breast cancer [J]. Pharmacol Res2020153:104683.
[56]
Rueda OMSammut SJSeoane JA,et al. Dynamics of breast-cancer relapse reveal late-recurring er-positive genomic subgroups [J]. Nature2019567(7748):399-404.
[57]
Devanand PSundaramoorthy SRyu MS,et al. Translational downregulation of Twist1 expression by antiproliferative gene,B-cell translocation gene 2,in the triple negative breast cancer cells [J]. Cell Death Dis201910(6):410.
[58]
Hata TRajabi HYamamoto M,et al. Targeting MUC1-C inhibits TWIST1 signaling in triple-negative breast cancer [J]. Mol Cancer Ther201918(10):1744-1754.
[59]
Wang SCSun HLHsu YH,et al. α-Linolenic acid inhibits the migration of human triple-negative breast cancer cells by attenuating Twist1 expression and suppressing Twist1-mediated epithelial-mesenchymal transition [J]. Biochem Pharmacol2020180:114152.
[60]
Giuli MVGiuliani EScrepanti I,et al. Notch signaling activation as a hallmark for triple-negative breast cancer subtype [J]. J Oncol20192019:8707053.
[61]
Zhong YShen SZhou Y,et al. Notch1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells [J]. Onco Targets Ther20169:6865-6871.
[62]
Valcourt DMDang MNScully MA,et al. Nanoparticle-mediated co-delivery of Notch-1 antibodies and ABT-737 as a potent treatment strategy for triple-negative breast cancer [J]. ACS Nano202014(3):3378-3388.
[63]
Garrido-Castro ACSpurr LFHughes ME,et al. Genomic characterization of de novo metastatic breast cancer [J]. Clin Cancer Res202127(4):1105-1118.
[64]
Zhang MMeng MLiu Y,et al. Triptonide effectively inhibits triple-negative breast cancer metastasis through concurrent degradation of Twist1 and Notch1 oncoproteins [J]. Breast Cancer Res202123(1):116.
[65]
Shao HMa JGuo T,et al. Triptolide induces apoptosis of breast cancer cells via a mechanism associated with the WNT/β-catenin signaling pathway [J]. Exp Ther Med20148(2):505-508.
[66]
Ou CCChen YWHsu SC,et al. Triptolide transcriptionally represses HER2 in ovarian cancer cells by targeting NF-κB [J]. Evid Based Complement Alternat Med20122012:350239.
[1] 陈庆秋, 钟玲, 张婷, 张孔涌, 桂余, 齐晓伟, 任林. IGF2BP2/CCNB2轴促进三阴性乳腺癌进展的机制研究[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(05): 287-295.
[2] 林丽, 杨英, 张嘉, 齐晓伟, 王莉, 王寅欢, 任林. 屈服应对方式在三阴性乳腺癌患者癌症复发恐惧与希望水平间的中介效应[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(04): 226-231.
[3] 卜烨, 王鹏, 安丽颖, 陈园. 三阴性乳腺癌组织长链非编码RNA CCAT1、miR-152表达与增殖侵袭基因以及临床病理特征的关系[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(04): 198-205.
[4] 赵长燕, 张明慧, 陆春燕. FOXC1和claudin-4在三阴性乳腺癌中的表达及其与肿瘤微环境和炎症相关因子的关系[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(02): 97-102.
[5] 刘伟, 牛云峰, 安杰. LINC01232 通过miR-516a-5p/BCL9 轴促进三阴性乳腺癌的恶性进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 330-338.
[6] 牛海刚, 郭文科. 三阴性乳腺癌组织中双特异性磷酸酶14与核受体相互作用蛋白1的表达及预后价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(04): 199-205.
[7] 麻凌峰, 张小杉, 魏颖, 张敏洁, 于超, 王雅晳. 中医药治疗类风湿关节炎的药效机制研究[J/OL]. 中华关节外科杂志(电子版), 2025, 19(06): 708-713.
[8] 杨娜, 胡刚, 潘越. 保乳术和改良根治术后行新辅助化疗对三阴性乳腺癌血清标志物影响[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(03): 345-348.
[9] 侯芳红, 贺修宝. 超声介导的雷公藤甲素外泌体靶向给药系统抗结直肠癌的应用评估[J/OL]. 中华消化病与影像杂志(电子版), 2026, 16(01): 13-20.
[10] 王鹏飞, 孙逸旸, 于岩瀑, 高树中. 高树中教授脐疗理论与临床应用[J/OL]. 中华针灸电子杂志, 2025, 14(04): 157-160.
[11] 程海波. 慢病防控视角下的“针药结合、增效减药”理念探讨[J/OL]. 中华针灸电子杂志, 2025, 14(03): 89-93.
[12] 张艳军. 针药并用的科学内涵与临床价值:机制创新与重大疾病防治的新路径[J/OL]. 中华针灸电子杂志, 2025, 14(03): 94-98.
[13] 尹巧英, 钱雅妮, 雷慧恩, 王石柳, 李婷婷, 尹瑞华, 卢璐. 针药结合治疗痰湿型多囊卵巢综合征肥胖:随机对照试验[J/OL]. 中华针灸电子杂志, 2025, 14(03): 99-103.
[14] 代培森, 郭东升, 张超, 刘爱峰, 薛宏飞, 王培检, 李文达, 高揆量. 针药并用治疗膝骨关节炎的研究进展[J/OL]. 中华针灸电子杂志, 2025, 14(03): 104-106.
[15] 马新童, 马铁明. 马铁明教授针药结合治疗偏头痛临床经验撷菁[J/OL]. 中华针灸电子杂志, 2025, 14(03): 111-114.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?