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ABT-737对顺铂耐药的乳腺癌细胞的杀伤作用及机制

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摘要 目的研究ABT-737是否能提高顺铂对耐药乳腺癌细胞株MDA-MB-231/R的杀伤活性并探讨其机制。方法采用顺铂梯度处理法构建顺铂耐药乳腺癌细胞株MDA-MB-231/R;采用MTT法检测ABT-737是否能增强顺铂对MDA-MB-231/R的杀伤活性;Western blot试验检测常规MDA-MB-231细胞及MDA-MB-231/R细胞Bcl-2,Bcl-xl及Bcl-w的表达水平;采用流式细胞术检测ABT-737联合顺铂对MDA-MB-231/R细胞的凋亡诱导效应及对线粒体膜电位的影响。结果顺铂对MDA-MB-231/R细胞的杀伤活性显著低于MDA-MB-231。联合ABT-737治疗后,顺铂对MDA-MB-231/R细胞的杀伤活性显著提高,与MDA-MB-231细胞相比,MDA-MB-231/R细胞的Bcl-2抗凋亡蛋白家族成员Bcl-w表达水平显著上调,但Bcl-2和Bcl-xl表达水平不受影响。ABT-737显著增强顺铂对MDA-MB-231/R细胞线粒体膜电位的损伤,促进细胞色素C的释放,进而诱导MDA-MB-231/R细胞发生凋亡。结论 ABT-737通过抑制Bcl-w的功能促进顺铂对耐药乳腺癌细胞的凋亡诱导效应。
出处 《浙江实用医学》 2016年第1期8-11,49,共5页 Zhejiang Practical Medicine
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