二甲双胍通过抑制NF-κB信号通路克服乳腺癌他莫昔芬获得性耐药  

Metformin reversed acquired resistance to tamoxifen in breast cancer by inhibiting NF-κB signaling pathway

作　　者：李羚 黄欣[1] 李妍[1] 胡梦笛 徐璐 LI Ling;HUANG Xin;LI Yan;HU Mengdi;XU Lu(Shandong Pediatric Drug Clinical Evaluation and R&D Researoh Center of Engineering Technology,Department of Clinical Pharmacy,The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,Jinan 250014,China;Department of Pharmacology and Chemical Biology,Shanghai Jiao Tong University School of Medicine,Shanghai 200021,China)

机构地区：[1]山东第一医科大学第一附属医院<山东省千佛山医院>临床药学,山东省儿童药物临床评价与研发工程技术研究中心,山东济南250014 [2]上海交通大学医学院药理学与化学生物学系,上海200021

出　　处：《药学研究》2024年第10期943-947,共5页Journal of Pharmaceutical Research

基　　金：国家自然科学基金项目(No.82104222);山东省自然科学基金项目(No.ZR2021QH247);山东省千佛山医院培育基金项目(No.QYPY2021NSFC0612);白求恩公益基金会(No.Z04JKM2023E040);山东省医学会齐鲁专项(No.YXH2022ZX02048)。

摘　　要：目的探讨二甲双胍克服乳腺癌他莫昔芬获得性耐药的作用及其机制。方法采用CCK-8和集落形成实验检测细胞增殖;采用流式细胞术检测细胞凋亡;采用Western blotting检测cleaved-PARP和核转录因子κB(NF-κB)p65的蛋白表达。免疫荧光分析用于检测NF-κB p65的核转位。结果我们发现二甲双胍能抑制乳腺癌细胞和他莫昔芬获得性耐药细胞的增殖并促进其凋亡。二甲双胍能够延缓乳腺癌细胞对他莫昔芬产生获得性耐药。此外,二甲双胍抑制了NF-κB信号通路。结论二甲双胍通过抑制NF-κB信号通路克服乳腺癌他莫昔芬获得性耐药,我们的研究为寻找克服他莫昔芬获得性耐药的治疗提供了潜在候选药物。Objective To explore the function and mechanism of metformin in overcoming acquired resistance to tamoxifen in breast cancer.Methods CCK-8 and colony formation assays were conducted to detect cell proliferation.Flow cytometry was employed to detect cell apoptosis.Western blotting was applied to detect the protein expression of cleaved-PARP and NF-κB p65.Immunofluorescence analysis was used to detected the NF-κB p65 nuclear translocation.Results We found that metformin inhibited proliferation and promoted apoptosis of breast cancer cells and acquired resistant cells.Metformin significantly delayed the emergence of acquired resistance to tamoxifen.In addition,metformin could inhibit NF-κB signaling pathway.Conclusion Metformin reversed acquired resistance to tamoxifen in breast cancer via NF-κB signaling pathway.Our study repurposes metformin as a potential candidate for overcoming acquired resistance to tamoxifen.

关 键 词：二甲双胍 乳腺癌 获得性耐药 他莫昔芬 核转录因子ΚB 

分 类 号：R979.1[医药卫生—药品]