基于miR-152-3p/Wnt轴辣椒素对乳腺癌他莫昔芬耐药细胞株LCC9耐药的作用机制  

Effect of Capsaicin on Drug Resistance of Breast Cancer Tamoxifen-Resistant Cell Line LCC9 through miR-152-3p/Wnt Pathway

作　　者：孙星 刘越[1] 赵得堡 盛晶[1] 刘扬帆[1] 刘丽娜[2] 屈中玉[1] 万里新[1] SUN Xing;LIU Yue;ZHAO Debao(Nanyang Central Hospital,Nanyang,473000)

机构地区：[1]南阳市中心医院,473000 [2]南阳市第二人民医院,473009

出　　处：《实用癌症杂志》2023年第10期1574-1578,共5页The Practical Journal of Cancer

基　　金：河南省医学科技攻关计划(联合共建)项目(编号:LHGJ20191463)。

摘　　要：目的探讨辣椒素对乳腺癌他莫西芬耐药细胞株LCC9耐药性的影响及其具体机制。方法不同浓度辣椒素处理LCC9细胞,CCK8法检测细胞存活率,qRT-PCR检测MCF-7和LCC9细胞中miR-152-3p和Wnt1 mRNA相对表达水平。将LCC9细胞分为对照组、inhibitor NC组(转染inhibitor NC)、inhibitor组(转染miR-152-3p inhibitor)、inhibitor+辣椒素组(转染miR-152-3p inhibitor 24 h后,200μmol/L辣椒素处理),CCK8法检测细胞存活率、qRT-PCR检测miR-152-3p相对表达水平、流式细胞仪检测细胞凋亡率、双荧光素酶报告基因法检测miR-152-3p与Wnt的靶向关系、蛋白印迹法检测β-连环蛋白(β-catenin)和T细胞因子4(TCF4)蛋白相对表达量。结果细胞存活率随辣椒素浓度的升高而降低(P<0.05)。LCC9细胞中miR-152-3p表达较MCF-7细胞降低,Wnt1 mRNA水平较MCF-7细胞升高(P<0.05)。与inhibitor NC组比较,inhibitor组细胞凋亡率、miR-152-3p表达水平降低,β-catenin和TCF4蛋白相对表达量升高(P<0.05);与inhibitor组比较,inhibitor+辣椒素组细胞存活率以及β-catenin和TCF4蛋白相对表达量降低,miR-152-3p表达水平和细胞凋亡率升高(P<0.05)。结论辣椒素可降低乳腺癌细胞对他莫西芬的耐药性,其可能是通过调节Wnt/β-catenin信号通路发挥作用。Objective To investigate the effect of capsaicin on drug resistance of breast cancer tamoxifen-resistant cell line LCC9 and its specific mechanism.Methods LCC9 cells were treated with different concentrations of capsaicin.The cell survival rate was detected by CCK8 method,and the relative expression levels of miR-152-3p and Wnt1 mRNA in MCF-7 and LCC9 cells were detected by qRT-PCR.LCC9 cells were divided into control group,inhibitor NC group(transfected with inhibitor NC),inhibitor group(transfected with miR-152-3p inhibitor),and inhibitor+capsaicin group(treated with 200μmol/L capsaicin 24 h after transfection with miR-152-3p inhibitor).The cell survival rate was detected by CCK8 method,the relative expression level of miR-152-3p was detected by qRT-PCR,the apoptosis rate was detected by flow cytometry,the targeting relationship between miR-152-3p and Wnt was detected by double lucifase reporter gene method,andβ-catenin and T cytokine 4 protein relative expression level(TCF4)were detected by western blot.Results The cell survival rate decreased with the increase of capsaicin concentration(P<0.05).The relative expression level of miR-152-3p was lower in LCC9 cells than MCF-7 cells,while Wnt1 mRNA expression level in LCC9 cells was higher than MCF-7 cells(P<0.05).Compared with the inhibitor NC group,the apoptosis rate and miR-152-3p expression levels in the inhibitor group were decreased,and the relative expression levels ofβ-catenin and TCF4 protein were increased(P<0.05).Compared with the inhibitor group,the cell survival rate and the relative expression levels ofβ-catenin and TCF4 protein were decreased in the inhibitor+capsaicin group,and the expression level of miR-152-3p and apoptosis rate were increased(P<0.05).Conclusion Capsaicin can reduce the resistance of breast cancer cells to tamoxifen,possibly by regulating the Wnt/β-catenin signaling pathway.

关 键 词：乳腺癌 耐药性 辣椒素 WNT/Β-CATENIN信号通路 

分 类 号：R737.9[医药卫生—肿瘤]