5氮-2’脱氧胞苷对人子宫内膜癌裸鼠移植瘤细胞凋亡及细胞周期的影响

Effect of 5-aza-CdR on Apoptosis and Cell Cycle of Endometrial Carcinoma Xenografted in Nude Mice

目的:研究5氮2′脱氧胞苷(5aza2′deoxycytidine,5azaCdR)对人子宫内膜癌裸鼠移植瘤细胞凋亡及细胞周期的影响,探讨其抗肿瘤效应可能的机制。方法:用子宫内膜癌裸鼠移植瘤模型SLI观察5azaCdR的抗肿瘤作用,逆转录-聚合酶链反应(reversetranscriptasepolymerasechainreaction,RTPCR)及流式细胞术检测裸鼠移植瘤用药后bax基因mRNA表达水平的改变及药物对细胞周期的影响。结果:用5azaCdR后,除裸鼠移植瘤p16基因甲基化水平逐渐降低以及mRNA表达恢复外,诱导baxmRNA的表达时间也长,但无明显G1期、G2/M期阻滞作用。结论:5azaCdR抑瘤作用的机理可能主要是通过p16基因去甲基化作用而使转录抑制去除,此外尚有诱导肿瘤细胞凋亡作用;在本实验条件下,该药对SLI细胞周期无明显影响。

Objective:This study was designed to evaluate t he antitumor effect and mechanism of5-aza-2' -deoxycytidine(5-aza-CdR)on apoptosis and cell cycle of endome trial carcinoma xenografted in nude mice.Methods :The effects of 5-aza-CdR on tumor growth inhibition were observed in endometrial carcinoma xenografted in nude mice.bax mRNA expression was determined by re verse transcriptase polymerase chain reaction(RT-PCR).Cell cycle was analyzed by flow cytometry.Results:The methylation level of p16gene gra dually decreased and the p16mRNA exp ression restored,bax mRNA expression was induced in ea rly stage,but G 1 or G 2 /M cell cycle arrest was not apparent after treatment with5-aza-CdR.Conclusion:The data show that 5-aza-CdR may inhi bit tumor growth by reactivating p16gene silenced by de novo methylation and inducing neopl astic cell apoptosis,and 5-aza-CdR didn't apparently to affect cell cycle of SL-I.