摘要
目的:探讨沉默交配型信息调节因子2同源蛋白1(silent mating type information regulation 2 homology 1,SIRT1)在宫颈癌化疗耐药中的作用及其机制。方法:体外培养人宫颈癌Hela细胞系和宫颈癌Hela/MMC耐药细胞亚系,western blotting检测MMC对Hela和Hela/MMC细胞内SIRT1蛋白表达的影响;MTT法检测MMC及Nicotinamide对Hela和Hela/MMC细胞增殖的影响;Annexin V-PI试验检测Hela/MMC细胞凋亡的亡的情况;RT-PCR方法检测耐药相关蛋白P-gp的mRNA表达情况。结果:正常情况下,Hela/MMC细胞中SIRT1的表达显著高于Hela细胞(P<0.05),MMC处理的Hela/MMC细胞中SIRT1的表达显著高于未经MMC处理(P<0.05)。Nicotinamide对Hela和Hela/MMC细胞具有相似的生长抑制作用,Nicotinamide可使MMC诱导的Hela/MMC细胞凋亡增加,同时降低细胞内P-gp的mRNA表达(P<0.05)。结论:SIRT1表达下调能显著减轻Hela/MMC细胞对MMC的耐药性,其作用可能与P-gp有关。
Objective： To discuss the role and mechanism of silent mating type information regulation 2 homology 1 （SIRT1） in cervical cancer drug resistance. Methods： Human cervical cancer Hela cell lines and cervical cancer Hela/MMC drug-resistant cell sublines were cultivated in vitro. The effects of MMC on SIRT1 protein expression was detected by Western blotting; MTT assay was used to detect the proliferative effect of Nicotinamide and MMC on Hela and Hela/MMC cells. Apoptotic cells were detected with Annexin V staining; mRNA of drug resistant-associated protein P-gp was measured by RT-PCR. Results： The expression of SIRT1 protein in Hela/MMC was significantly higher than that in Hela cells normally （P〈0.05） and the expression of SIRT1 protein in Hela/MMC MMC-treatment group was significantly higher than that in control （P〈0.05）; SIRT1 inhibitors Nicotinamide exhibited the similar growth-inhibitory effects on Hela and Hela/MMC, which can induce the increase of Hela/MMC cell apoptosis and also reduce the mRNA level of P-gp （P〈0.05）. Conclusion： The downregulation of SIRT1 can significantly mitigate MMC- resistance of MMC-Hela, which may be achieved by regulated P-gp expression.
出处
《现代生物医学进展》
CAS
2013年第24期4654-4657,共4页
Progress in Modern Biomedicine
关键词
SIRT1
烟酰胺
宫颈癌
耐药
SIRT1
Nicotinamide
Cervical cancer
Drug resistance
