马里苷靶向p38α增强卵巢癌细胞对DNA损伤药物敏感度的研究  

Marein Increases Sensitivity of Ovarian Cancer Cells to DNA Damage Drugs by Targeting p38α

作　　者：曹玉敏 郭凡凡 王芳[1] 张熠[2] 陈友国[1] CAO Yumin;GUO Fanfan;WANG Fang(Department of Obstetrics and Gynecology,First Affiliated Hospital of Soochow University,Jiangsu 215006,China)

机构地区：[1]苏州大学附属第一医院妇产科,215006 [2]苏州大学药学院,215123

出　　处：《医学研究杂志》2024年第3期43-49,共7页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81973352,82273944)。

摘　　要：目的探究马里苷抑制同源重组修复,联合使用DNA损伤药物的疗效以及其机制。方法CCK-8法、克隆集落形成实验、类器官药敏实验检验细胞和类器官在联合用药后的增敏情况;Western blot法、彗星实验以及同源重组修复报告基因检测细胞联合用药后的DNA损伤情况及其抑制同源重组修复的机制;细胞热转移实验和药物亲和反应的靶点稳定性技术验证马里苷与p38α的结合情况。结果马里苷与p38α结合增加了癌细胞和类器官对DNA损伤药物的敏感度;马里苷抑制p-p38α,增加癌细胞的DNA损伤,抑制癌细胞同源重组修复。结论马里苷抑制同源重组修复,增强了癌细胞对DNA损伤药物的敏感度,从而为卵巢癌的临床用药提供了新策略。Objective To investigate the efficacy and mechanism of marein combined with DNA damage drugs by inhibiting homologous recombination repair.Methods CCK-8method,clonal colony formation assay and organoid drug sensitivity test were used to detect the sensitization of marein combined with DNA damage drugs.Western blot,comet assay and homologous recombination repair reporter gene were used to detect the DNA damage and the mechanism of inhibiting the homologous recombination repair.The binding of marein to p38αwas confirmed by cell heat transfer assay and target stability technique of drug affinity reaction.Results Marein increased the susceptibility of cancer cells and organoids to DNA damage drugs by binding to p38α.By inhibiting p-p38α,marein increased DNA damage of cancer cells,and inhibited the homologous recombination repair of cancer cells.Conclusion Marein enhances the sensitivity of cancer cells to DNA damage drugs by inhibiting homologous recombination repair,which provides a new strategy for clinical use of ovarian cancer.

关 键 词：马里苷 同源重组修复 p38α 

分 类 号：R737.31[医药卫生—肿瘤]