【摘 要】
：
研究背景:多药耐药(multiple drug resistance,MDR)是肿瘤逃避治疗的机制之一,DEDD作为促凋亡因子,其可通过与PI3KC3/Beclin1复合物相互作用激活自噬,进而促进自噬相关Snail/Twist降解,抑制/逆转EMT进程. 目的:研究DEDD基因在MCF-7细胞肿瘤耐药中的作用,为乳腺癌的治疗提供新的策略和实验依据.方法:MTS法检测不同浓度及作用时间的阿霉素、紫
【机 构】
：
武警后勤学院附属医院 武警后勤学院救援医学系
【出 处】
：
第一届自噬生物学与疾病国际研讨会(The 1st International Symposium on Autophag
论文部分内容阅读
研究背景:多药耐药(multiple drug resistance,MDR)是肿瘤逃避治疗的机制之一,DEDD作为促凋亡因子,其可通过与PI3KC3/Beclin1复合物相互作用激活自噬,进而促进自噬相关Snail/Twist降解,抑制/逆转EMT进程. 目的:研究DEDD基因在MCF-7细胞肿瘤耐药中的作用,为乳腺癌的治疗提供新的策略和实验依据.方法:MTS法检测不同浓度及作用时间的阿霉素、紫杉醇对MCF-7细胞活力的影响,流式检测阿霉素、紫杉醇对MCF-7细胞凋亡的影响,PCR,Western Blot检测BCL-2家族蛋白及基因的表达. 结果:阿霉素、紫杉醇干预24h、48h后,MCF-7 DEDD-shRNA细胞存活率显著高于WT和control shRNA细胞,细胞凋亡率显著低于WT和control shRNA细胞.进一步检测发现,MCF-7 DEDD-shRNA细胞的BCL-2蛋白及基因表达显著低于control shRNA细胞,Bcl-xl、Bak、Bax蛋白表达二者则无显著差异.应用不同浓度ABT-199作用于MCF-7 control shRNA及DEDD-shRNA细胞,发现DEDD-shRNA细胞对ABT-199的杀伤作用更加敏感. 结论:DEDD低表达的乳腺癌细胞对于传统的化疗药物具有更强的耐药性,而对于BCL-2抑制剂的作用则更加敏感.因此,对于DEDD低表达的乳腺癌患者可考虑应用BCL-2抑制剂进行联合化疗.
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