【摘要】 目的:探讨DNA甲基化抑制剂5-aza-2′-deoxycitydine(5-aza-dC)影响胃癌细胞MGC803对奥沙利铂(Oxaliplatin,OXA)的化疗敏感性,及其与Ⅱ相代谢解毒酶GSTP1表达的相关性。方法:5-aza-dC处理MGC803,RT-PCR和Western-Blot方法检测GSTP1基因mRNA和蛋白表达。MSP法分析GSTP1基因启动子区甲基化状态。MTT法检测药物敏感性。结果:5-aza-dC诱导GSTP1基因启动子去甲基化,上调GSTP1mRNA和蛋白表达,降低了MGC803细胞对OXA的敏感性,24h IC50值分别为对照组(13.15±1.7)μg/L、1μM 5-aza-dC处理组(24.54±2.1)μg/L、5μM 5-aza-dC处理组(30.81±1.3)μg/L及10μM 5-aza-dC处理组(51.72±1.6)μg/L,P值<0.01,差异有统计学意义。结论:5-3za-dC降低胃癌细胞对奥沙利铂的敏感性,其机制与增强GSTP1表达有关。更多还原

【Abstract】 Objective:To explore the effect of 5-aza-2’-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferase, on the sensitivity of human gastric cancer cell line MGC803 cells to oxaliplatin and its relationship with GSTP1. Methods:MGC803 cells were treated with 5-aza-dC. The expression of GSTP1 mRNA was detected using reverse transcription PCR (RT-PCR). Protein expression was analyzed by Western blot. DNA methylation status of the GSTP1 gene promoter was assayed by methylation-specific PCR (MSP). Drug sensitivity was detected by MTT method. Results:5-aza-dC induced demethylation of the GSTP1 gene promoter. GSTP1 mRNA and protein expression were markedly upregulated by 5-aza-dC treatment by the 5th day. The 24 hour IC50s of the control group, the 1μM 5-aza-dC treatment group, the 5μM 5-aza-dC treatment group and the 10μM 5-aza-dC treatment group were (13.15±1.7)μg/L, (24.54±2.1)|μg/L, (30.81±1.3)μg/L and (51.72±1.6)μg/L, with a significant difference among the treatment groups (P<0.01). Conclusion:5-aza-dC decreases the sensitivity of gastric cancer cells to oxaliplatin through a mechanism related to an increase in GSTP1 expression.更多还原