靶向survivin反义寡核苷酸对MCF-7乳腺癌细胞系survivin mRNA及紫杉醇药物敏感性的影响

目的探讨靶向survivin基因的反义寡核苷酸（ASODN）对MCF 7细胞的增殖、凋亡及药物敏感性等生物学行为的影响。 方法采用脂质体介导survivin ASODN转染MCF-7乳腺癌细胞系，RT-PCR检测survivin mRNA的表达，MTT法检测细胞增殖能力及对药物的敏感性，流式细胞术检测细胞周期及细胞凋亡。 结果survivin ASODN可有效下调survivin表达水平，抑制细胞的生长，并呈时间剂量依赖关系；流式细胞术示，24h反义转染组细胞周期被阻滞于G₂/M期，细胞凋亡率增加到15.23%。 紫杉醇作用早期（6h），survivin mRNA 表达增高，利于肿瘤细胞逃避紫杉醇诱导的细胞凋亡，增加肿瘤耐药机会；反义转染组中细胞早期survivin mRNA表达上调受到抑制，对药物的敏感性增加。 结论survivin基因ASODN转染细胞后，下调survivin的表达，细胞凋亡增加，提高了对药物的敏感性。

Effects of the survivin antisense oligonucleotide on survivin mRNA expression and chemosensitivity to Paclitaxel in human breast cancer cells MCF-7

Objective To investigate the effects of the survivin antisense oligonucleotide(ASODN) on cell proliferation,apoptosis and chemosensitivity to paclitaxel in human breast cancer cells MCF-7.Methods Survivin-ASODN was transfected into MCF-7cells mediated by Lip reagent.The expression of survivin mRNA was determined by RT-PCR,cell proliferation and chemosensitivity to paclitaxel in MCF-7 were determined by MTT assay,and apoptosis and cell cycle were determined by flow cytometry.Results The antisense compound efficiently down-regulated survivin mRNA expression in a time-dependent manner.The growth inhibition rate of MCF-7 was decreased in a dose-and time-independent manner.The cell cycle was arrested at G2/M phase;apoptosis was obviously found.Paclitaxel could enhance the expression of survivin at an early time,and this effect might play a critical role in the escape to apoptosis induced by paclitaxel,which may promote the resistance of paclitaxel.The antisense compound efficiently down-regulated this induction by paclitaxel,and enhanced the chemosensitivity to paclitaxel in MCF-7. Conclusion Survivin antisense oligonucleotide effectively suppresses the expression of survivin mRNA,increases apoptosis and enhances the chemosensitivity to paclitaxel in MCF-7.