专题笔谈

毛兰素诱导乳腺癌细胞凋亡的机制及治疗潜力的研究进展

  • 李京朔 ,
  • 刘首诗 ,
  • 郭宏伟
展开
  • 1.广西医科大学第一临床医学院 (广西 南宁 530021 )
    2.长寿与老年相关疾病教育部重点实验室,广西医科大学转化医学研究中心 (广西 南宁 530021 )
    3.广西生物活性分子研究与评价重点实验室,广西医科大学药学院 (广西 南宁 530021 )
郭宏伟,博士,教授,博士研究生导师。入选国家青年岐黄学者。美国密歇根大学和澳大利亚墨尔本大学访问学者,现担任中国中药协会中药发酵药物专委会副主委,中华中医药学会中药基础理论分会常务委员,中国民族医药学会方药量效研究分会常务理事等。兼任“广西中药组效学重点研究室”主任和“广西生物活性分子研究与评价”重点实验室常务副主任。先后主持国家自然科学基金、广西重点研发项目、广西自然科学基金重点项目等课题27项。以通信作者在《Med Res Rev》《Pharmacol Res》《Int J Biol Macromol》等国际期刊发表SCI收录论文40余篇。出版教材和学术专著8部。授权国家发明专利12项,实施成果转化1项,牵头制定行业标准2项,以第一完成人获广西自然科学二等奖1项,中国民族医药学会科学技术二等奖1项,目前担任《环球中医药》和《中国癌症防治杂志》编委,《Chin Med》、《Chin J Nat Med》和《Chin Herb Med》等SCI杂志青年编委等。

收稿日期: 2025-04-16

  网络出版日期: 2025-07-29

基金资助

国家自然科学基金项目(82074347)

Advances in the mechanism and therapeutic potential of Erianin⁃induced apoptosis in breast cancer cells

  • Jingshuo LI ,
  • Shoushi LIU ,
  • Hongwei. GUO
Expand
  • 1.The First Clinical Medical School,Guangxi Medical University,Nanning 530021,Guangxi,China
    2.Key Laboratory of Longevity and Aging?related Diseases of Chinese Ministry of Education,Center for Translational Medicine,Guangxi Medical University,Nanning 530021,Guangxi,China

Received date: 2025-04-16

  Online published: 2025-07-29

摘要

该综述系统探讨了来源于传统中药石斛的活性成分毛兰素在乳腺癌,尤其是三阴性乳腺癌(TNBC)治疗中的研究进展。作为缺乏雌激素受体(estrogen receptor, ER)、孕激素受体(PR)及人表皮生长因子受体2(HER2)表达的侵袭性亚型,TNBC因治疗靶点匮乏,治疗选择有限,临床仍主要依赖传统化疗方案。毛兰素通过诱导乳腺癌细胞凋亡展现了显著的抗癌潜力,其作用机制主要包括通过激活内源性和外源性凋亡途径,特别是线粒体功能紊乱介导的细胞色素c释放和半胱天冬酶(caspase)依赖性途径的激活,从而增强癌细胞对死亡信号的敏感性。在分子水平,毛兰素在调节磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、丝裂原活化蛋白激酶(MAPK)和活化T细胞核因子1(NFATc1)等关键致癌通路方面表现出显著效果,能够抑制细胞增殖、迁移及诱导细胞凋亡。然而,尽管毛兰素具有良好的抗癌效果,其开发仍面临溶解度差和生物利用度低等挑战。因此,探索毛兰素与化疗药物的协同作用及作为放射增敏剂的潜力成为提升临床应用价值的重要研究方向。值得关注的是,毛兰素通过重塑凋亡调控网络(如调节Bax/Bcl-2蛋白比例)克服TNBC耐药性的独特优势,使其成为极具前景的多靶点治疗候选药物。目前大多数证据来自体外和动物实验,未来需通过人类临床试验进一步验证其疗效和安全性,并结合纳米递送系统优化、结构衍生物开发等策略改善药代动力学特性。本综述系统梳理毛兰素诱导凋亡的核心机制及治疗潜力,为开发针对TNBC的创新治疗方案提供理论依据。

本文引用格式

李京朔 , 刘首诗 , 郭宏伟 . 毛兰素诱导乳腺癌细胞凋亡的机制及治疗潜力的研究进展[J]. 实用医学杂志, 2025 , 41(14) : 2132 -2137 . DOI: 10.3969/j.issn.1006-5725.2025.14.002

Abstract

This review systematically elucidates recent advances in the therapeutic application of Erianin, a natural compound derived from Dendrobium, a traditional Chinese medicine, in the treatment of breast cancer, with particular emphasis on triple-negative breast cancer (TNBC). TNBC is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, which presents significant clinical challenges due to limited therapeutic targets and continued reliance on conventional chemotherapy. Erianin exhibits notable anticancer potential through the induction of apoptosis in breast cancer cells. Its primary mechanisms involve sensitizing cancer cells to apoptotic signals via activation of both intrinsic and extrinsic apoptotic pathways, particularly through mitochondrial dysfunction-mediated cytochrome c release and subsequent activation of caspase-dependent pathways. At the molecular level, Erianin effectively modulates key oncogenic signaling pathways, including PI3K/Akt, MAPK, and NFATc1 cascades, thereby suppressing cell proliferation and migration while promoting apoptosis. However, current research priorities center on investigating its synergistic effects with chemotherapeutic agents and assessing its radiosensitization potential to further enhance its clinical utility. Notably, Erianin demonstrates unique advantages in overcoming drug resistance in TNBC by modulating apoptotic regulatory networks, particularly through regulation of the Bax/Bcl-2 protein ratio, positioning it as a promising multi-target therapeutic candidate. Although existing evidence largely stems from in vitro and animal studies, future research should prioritize human clinical trials to validate its efficacy and safety, alongside pharmaceutical optimization strategies such as the development of nanodelivery systems and exploration of structural derivatives. This review systematically clarifies the core mechanism and therapeutic potential of pilanin-induced apoptosis, and provides theoretical basis for developing innovative therapeutic regimens for TNBC.

参考文献

[1] 王培宇, 黄祺, 王少东, 等. 《全球癌症统计数据2022》要点解读 [J]. 中国胸心血管外科临床杂志, 2024, 31(7): 933-954.
[2] 邓雅倩, 李文肖, 徐泽林, 等. 生长方位量化联合S-Detect技术对乳腺癌腋窝淋巴结转移的预测价值 [J]. 实用医学杂志, 2025, 41(1): 100-107.
[3] 宋子旭, 朱光正, 郭晨旭, 等. SLC35A2、前叶黄素亚基2在乳腺癌中的表达及其与临床观察指标和预后的关系 [J]. 实用医学杂志, 2024, 40(4): 496-502.
[4] YIN L, DUAN J J, BIAN X W, et al. Triple-negative breast cancer molecular subtyping and treatment progress [J]. Breast Cancer Res, 2020, 22(1): 61. doi:10.1186/s13058-020-01296-5
[5] JIAO Q, WU A, SHAO G, et al. The latest progress in research on triple negative breast cancer (TNBC): Risk factors, possible therapeutic targets and prognostic markers [J]. J Thorac Dis, 2014, 6(9): 1329-35.
[6] 黄翠霞, 张雅倩, 杨爱萍, 等. 基于Hippo/YAP信号通路探讨穿心莲内酯抗三阴性乳腺癌的作用机制 [J]. 实用医学杂志, 2023, 39(16): 2050-2056. doi:10.3969/j.issn.1006-5725.2023.16.007
[7] LEON-FERRE R A, GOETZ M P. Advances in systemic therapies for triple negative breast cancer [J]. BMJ, 2023, 381: e071674. doi:10.1136/bmj-2022-071674
[8] CETIN I, TOPCUL M. Triple negative breast cancer [J]. Asian Pac J Cancer Prev, 2014, 15(6): 2427-2431. doi:10.7314/apjcp.2014.15.6.2427
[9] FREMD C, JAEGER D, SCHNEEWEISS A. Targeted and immuno-biology driven treatment strategies for triple-negative breast cancer: Current knowledge and future perspectives [J]. Expert Rev Anticancer Ther, 2019, 19(1): 29-42. doi:10.1080/14737140.2019.1537785
[10] TONG L, YU X, WANG S, et al. Research Progress on Molecular Subtyping and Modern Treatment of Triple-Negative Breast Cancer [J]. Breast Cancer (Dove Med Press), 2023, 15: 647-658. doi:10.2147/bctt.s426121
[11] GARUFI G, PALAZZO A, PARIS I, et al. Neoadjuvant therapy for triple-negative breast cancer: potential predictive biomarkers of activity and efficacy of platinum chemotherapy, PARP- and immune-checkpoint-inhibitors [J]. Expert Opin Pharmacother, 2020, 21(6): 687-699. doi:10.1080/14656566.2020.1724957
[12] HONG J, XIE Z, YANG F, et al. Erianin suppresses proliferation and migration of cancer cells in a pyruvate carboxylase-dependent manner [J]. Fitoterapia, 2022, 157: 105136. doi:10.1016/j.fitote.2022.105136
[13] DONG H, WANG M, CHANG C, et al. Erianin inhibits the oncogenic properties of hepatocellular carcinoma via inducing DNA damage and aberrant mitosis [J]. Biochem Pharmacol, 2020, 182: 114266. doi:10.1016/j.bcp.2020.114266
[14] YANG Z, LIU R, QIU M, et al. The roles of ERIANIN in tumor and innate immunity and its' perspectives in immunotherapy [J]. Front Immunol, 2023, 14: 1170754. doi:10.3389/fimmu.2023.1170754
[15] KOCOGLU S S, SE?ME M, SUNAY F B. Erianin as a Promising Novel Agent in the Treatment of Neuroblastoma: The Anticancer Effects and Underlying Molecular Mechanisms [J]. Anticancer Agents Med Chem, 2023, 23(10): 1204-1210. doi:10.2174/1871520623666230228095429
[16] LIU Z, HUANG L, SUN L, et al. Ecust004 Suppresses Breast Cancer Cell Growth, Invasion, and Migration via EMT Regulation [J]. Drug Des Devel Ther, 2021, 15: 3451-3461. doi:10.2147/dddt.s309132
[17] MA L, LI M, ZHANG Y, et al. Recent advances of antitumor leading compound Erianin: Mechanisms of action and structural modification [J]. Eur J Med Chem, 2023, 261: 115844. doi:10.1016/j.ejmech.2023.115844
[18] LI M, ZHAO Y, LI H, et al. Mechanism of Erianin anti-triple negative breast cancer based on transcriptomics methods and network pharmacology [J]. Aging (Albany NY), 2024, 16(3): 2848-2865.
[19] MANIAM S, MANIAM S. Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells [J]. Int J Mol Sci, 2021, 22(18):9722. doi:10.3390/ijms22189722
[20] FU B, LOU Y, WU P, et al. Emerging role of necroptosis, pyroptosis, and ferroptosis in breast cancer: New dawn for overcoming therapy resistance [J]. Neoplasia, 2024, 55: 101017. doi:10.1016/j.neo.2024.101017
[21] YAN L, ZHANG Z, LIU Y, et al. Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology [J]. Front Mol Biosci, 2022, 9: 862932. doi:10.3389/fmolb.2022.862932
[22] 裴彩霞,贾楠,刘俊伶,等. 细胞死亡的多种方式及其机制研究进展[J/OL]. 解放军医学杂志,1-17[2025-04-16]..
[23] GAO J, SANA R, CALDER V, et al. Mitochondrial permeability transition pore in inflammatory apoptosis of human conjunctival epithelial cells and T cells: Effect of cyclosporin A [J]. Invest Ophthalmol Vis Sci, 2013, 54(7): 4717-4733. doi:10.1167/iovs.13-11681
[24] HU S, GAO Y, ZHOU H, et al. New insight into mitochondrial changes in vascular endothelial cells irradiated by gamma ray [J]. Int J Radiat Biol, 2017, 93(5): 470-476. doi:10.1080/09553002.2017.1286048
[25] 黄智超, 李国峰, 郎一帆, 等. 中药诱导肺癌细胞凋亡机制的研究进展 [J]. 中国实验方剂学杂志, 2021, 27(23): 226-236.
[26] DAS C K, LINDER B, BONN F, et al. BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells [J]. Neoplasia, 2018, 20(3): 263-279. doi:10.1016/j.neo.2018.01.001
[27] WEI X, LIU Q, LIU L, et al. Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway [J]. Int J Mol Sci, 2024, 25(14):7973. doi:10.3390/ijms25147973
[28] HUANG Y, JIAO Z, FU Y, et al. An overview of the functions of p53 and drugs acting either on wild- or mutant-type p53 [J]. Eur J Med Chem, 2024, 265: 116121. doi:10.1016/j.ejmech.2024.116121
[29] YAN W, ZHOU Y, YUAN X, et al. The cytotoxic natural compound erianin binds to colchicine site of β-tubulin and overcomes taxane resistance [J]. Bioorg Chem, 2024, 150: 107569. doi:10.1016/j.bioorg.2024.107569
[30] YANG A, SUN Z, LIU R, et al. Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress [J]. Front Oncol, 2021, 11: 727605. doi:10.3389/fonc.2021.727605
[31] MEZA-SOSA K F, MIAO R, NAVARRO F, et al. SPARCLE, a p53-induced lncRNA, controls apoptosis after genotoxic stress by promoting PARP-1 cleavage [J]. Mol Cell, 2022, 82(4): 785-802.e10. doi:10.1016/j.molcel.2022.01.001
[32] GUO Z, LUO J, MASHL R J, et al. Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models [J]. Cancer Res Commun, 2024, 4(6): 1430-1440. doi:10.1158/2767-9764.crc-24-0047
[33] FENG Y, WU Z, LIU H, et al. Combining photodynamic therapy and ATM inhibition using modified bovine serum albumin: A co-delivery nano platform for eliciting pyroptosis and apoptosis to fuel TNBC therapy [J]. Int J Biol Macromol, 2025, 307(Pt 4): 142140. doi:10.1016/j.ijbiomac.2025.142140
[34] ZHANG X, WANG Y, LI X, et al. The anti-carcinogenesis properties of erianin in the modulation of oxidative stress-mediated apoptosis and immune response in liver cancer [J]. Aging (Albany NY), 2019, 11(22): 10284-10300. doi:10.18632/aging.102456
[35] KAWAMOTO Y, AYAKI T, URUSHITANI M, et al. Activated caspase-9 immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy [J]. Neurosci Lett, 2016, 628: 207-212. doi:10.1016/j.neulet.2016.06.036
[36] 李震, 曹奕鸥, 肖立俊, 等. 毛兰素及其衍生物抗肿瘤作用研究进展 [J]. 中成药, 2019, 41(10): 2442-2444.
[37] XIE H, FENG S, FARAG M A, et al. Synergistic cytotoxicity of erianin, a bisbenzyl in the dietetic Chinese herb Dendrobium against breast cancer cells [J]. Food Chem Toxicol, 2021, 149: 111960. doi:10.1016/j.fct.2020.111960
[38] TANG L, RUAN Y, WANG B, et al. Erianin inhibits the progression of DDP-resistant lung adenocarcinoma by regulating the Wnt/β-catenin pathway and activating the caspase-3 for apoptosis in vitro and in vivo [J]. Hereditas, 2024, 161(1): 48. doi:10.1186/s41065-024-00351-x
[39] LAM F, BRADSHAW T D, MAO H, et al. ZJU-6, a novel derivative of Erianin, shows potent anti-tubulin polymerisation and anti-angiogenic activities [J]. Invest New Drugs, 2012, 30(5): 1899-1907. doi:10.1007/s10637-011-9755-9
[40] MIAO Q, DENG W Q, LYU W Y, et al. Erianin inhibits the growth and metastasis through autophagy-dependent ferroptosis in KRAS(G13D) colorectal cancer [J]. Free Radic Biol Med, 2023, 204: 301-312. doi:10.1016/j.freeradbiomed.2023.05.008
[41] SHENG Y, CHEN Y, ZENG Z, et al. Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming [J]. J Med Chem, 2022, 65(1): 460-484.
[42] ZHU Q, SHENG Y, LI W, et al. Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits bladder cancer cell growth via the mitochondrial apoptosis and JNK pathways [J]. Toxicol Appl Pharmacol, 2019, 371: 41-54. doi:10.1016/j.taap.2019.03.027
[43] FAN Y, HE S. The Characteristics of Tumor Microenvironment in Triple Negative Breast Cancer [J]. Cancer Manag Res, 2022, 14: 1-17. doi:10.2147/cmar.s316700
[44] LI G, ZHANG H, LAI H, et al. Erianin: A phytoestrogen with therapeutic potential [J]. Front Pharmacol, 2023, 14: 1197056. doi:10.3389/fphar.2023.1197056
[45] 舒波, 甘鸿川, 出良钊,等. 载药纳米递送系统在胶质瘤治疗中的研究进展 [J]. 实用医学杂志, 2022, 38(16): 1993-1997.
文章导航

/