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作 者:莫志强[1] 涂刚[1] 罗浩军[1] 李振华[1] 杨光伦[1]
机构地区:[1]重庆医科大学附属第一医院内分泌乳腺外科,重庆400016
出 处:《第三军医大学学报》2011年第21期2256-2259,共4页Journal of Third Military Medical University
基 金:国家自然科学基金面上项目(81072149)~~
摘 要:目的构建人乳腺癌细胞MCF-7他莫昔芬(Tamoxifen,TAM)耐药细胞模型,并鉴定其耐药性。方法采用高浓度短时间4-羟他莫昔芬(4-hydroxytamoxifen,OHT)冲击法,诱导人乳腺癌MCF-7/TAM耐药细胞株。通过细胞形态学观察、生长曲线、细胞倍增时间、药物毒性实验、细胞周期及凋亡相关蛋白BIK和Caspase-7的检测,评价MCF-7/TAM耐药细胞株的耐药性。结果成功构建MCF-7/TAM耐药细胞株,其耐药指数(resistance index,RI)为(13.88±2.93)(P<0.05)。与其母细胞相比,MCF-7/TAM耐药细胞株不仅细胞形态发生了变化,生长增殖能力增强(P<0.05),细胞倍增时间缩短(P<0.05),而且对OHT介导的毒性效应有较强的抵抗能力(P<0.05),OHT不能促进MCF-7/TAM耐药细胞内BIK和Caspase-7蛋白的表达(P<0.05)。结论通过高浓度短时间OHT冲击法诱导的MCF-7/TAM耐药细胞株对TAM产生一定的耐药性。Objective To establish a Tamoxifen(TAM)-resistant cell line of MCF-7 human breast cancer and to investigate the drug resistance of the cell line.Methods MCF-7 Tamoxifen-resistant(MCF-7/TAM-R) cell line was induced by a high concentration of 4-hydroxytamoxifen(OHT) treatment for a short period.Drug resistance of MCF-7/TAM-R cells were determined by cell morphology,cell growth curve,cell doubling time,drug toxicity tests,cell cycle and expression of apoptosis-related proteins BIK and Caspase-7.Results MCF-7/TAM-R cell line was successfully established,and its drug resistance index(RI) was 13.88±2.93(P〈0.05).Compared with its parental cell line,MCF-7/TAM-R cell line exhibited a different cell morphology,a higher proliferation ability(P〈0.05),a shorter cell doubling time(P〈0.05) and a stronger resistance to OHT-mediated cytotoxic effects(P〈0.05).OHT failed to induce the expression of BIK and Caspase-7(P〈0.05) in MCF-7/TAM-R cell line.Conclusion MCF-7/TAM-R cell line induced by a high concentration of OHT for a short period has a significant resistance to TAM.
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