反义寡核苷酸抑制survivin表达来增强乳腺癌细胞株MCF-7和MDA-MB-231对多西他赛敏感性的研究

Antisense oligonucleotide inhibits sensitivity of human breast cancer cells MCF-7 and MDA-MB-231 to docetaxel

目的:探讨利用反义寡核甘酸(ASODN)技术封闭乳腺癌细胞株survivin基因,观察survivin基因表达下调能否诱导细胞凋亡及增强对多西他赛(docetaxel)药物敏感性。方法:Survivin ASODN单独及联合多西他赛处理乳腺癌细胞株MCF-7和MDA-MB-231,RT-PCR检测survivin mRNA的表达,免疫细胞化学方法和W estern b lotting检测survivin蛋白表达,倒置显微镜观察细胞形态变化,MTT法检测细胞的生长抑制率。结果:Survivin ASODN可下调人乳腺癌细胞株中survivin mRNA和蛋白质的表达;survivin ASODN与多西他赛联合用药组相比对照组和多西他赛组可明显抑制细胞株的生长(P<0.01)。结论:Survivin ASODN明显抑制survivin基因在乳腺癌细胞株MCF-7和MDA-MB-231中的转录及翻译,明显提高乳腺癌对多西他赛的敏感性。

Objective Through interfering the expression of survivin with survivin ASODN,to of downregulation of survivin on cell apoptosis and chemosensitivity to docetaxel in breast cancer c investigate the effect ells. Methods The one or together. The n was tested with immunocytochemistry and Western blotting analysis. Cell morphological transformation was observed with inverted microscope. The inhibitive rates of the ceils was determined by MTT. Results Survivin ASODN could down-regulate the expression of survivin. The growth of breast cancer cells can be significantly inhibited by combined survivin ASODN and docetaxel group. The effect was higher than that of control and docetaxel group （ P〈0.01 ）. Conclusion These results show that by survivin ASODN, survivin expression can be effectively decreased at both transcriptional and translational level. The reduction of survivin expression exerts significant effects on chemosensitivity of breast cancer cells MCF-7 and MDA-MB-231 to docetaxel.