Snail促进乳腺癌MCF-7细胞移植瘤对多柔比星的耐药及其机制

目的:探讨Snail在乳腺癌MCF-7细胞移植瘤对多柔比星耐药中的作用及其可能的机制.方法:构建Snail基因真核表达载体pcDNA3.1-Snail,转染至MCF-7细胞,筛选稳定表达Snail的MCF-7/Snail细胞,以转染空质粒pcDNA3.1的MCF-7细胞(MCF-7/pcDNA)为对照.构建小鼠MCF-7/Snail及MCF-7/pcDNA细胞移植瘤模型,注射多柔比星,观测移植瘤生长,计算抑瘤率.免疫组织化学方法检测移植瘤组织中Snail、多药耐药基因-1(muhidrug resistance-1,MDR-1)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达.结果:成功构建pcDNA3.1-Snail表达载体,转染MCF-7细胞后获得MCF-7/Snail和MCF-7/pcDNA细胞,并制备小鼠移植瘤.多柔比星治疗后,MCF-7/Snail细胞移植瘤的瘤重明显高于MCF-7/pcDNA细胞移植瘤[(1.413±0.674)gvs(1.257±0.576)g,P＜0.05],多柔比星对MCF-7/Snail移植瘤抑瘤率明显低于MCF-7/pcDNA移植瘤(18.42% vs 30.18%,P＜0.05),MCF-7/Snail细胞移植瘤的组织中Snail、MDR-1、MMP-9的表达均显著高于MCF-7/peDNA移植瘤(408.08±20.39 vs 67.67±16.56,363.50±26.56 vs 55.08±12.23,396.25±16.03 vs 56.92±7.35;均P＜0.01),且Snail与MDR-1和MMP-9的表达均呈正相关(r1=0.89,P＜0.01;r2=0.81,P＜0.01).结论:Snail促进乳腺癌MCF-7细胞移植瘤埘多柔比星的耐药,其机制与增强MDR-1和MM9-9表达有关.