5-氮杂-2′-脱氧胞苷、曲古抑菌素A联合化疗对人胃癌细胞生长及MGMT基因表达的影响

Effects of combined use of 5-aza-2′-deoxycytidine and trichostatin A on the growth of human gastric cancer cell line and MGMT expression

目的探讨体外5-氮杂-2′-脱氧胞苷(5-AzadC)、曲古抑菌素A(TSA)联合5-氟尿嘧啶(5-FU)和紫杉醇(PTX)对人胃癌SGC-7901细胞生长及6-氧-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因表达的影响。方法将培养的SGC-7901细胞分为八组:对照组、5-FU+PTX组、5-AzadC组、TSA组、5-AzadC+TSA组、5-AzadC+5-FU+PTX组、TSA+5-FU+PTX组和5-AzadC+TSA+5-FU+PTX组。用MTS法测定各组药物对SGC-7901细胞生长的影响,RT-PCR和Western blot方法检测SGC-7901细胞MGMT mRNA及其蛋白的表达。结果 5-AzadC、TSA、5-FU+PTX均能抑制细胞生长,且呈时间依赖性,多药联合组较单药组抑制率增强(P<0.05);加药72h后多药联合组较单药组MGMT mRNA和蛋白表达增强(P<0.05)。结论 5-AzadC、TSA、5-FU+PTX及药物联合干预通过增强MGMT基因再表达而抑制人胃癌SGC-7901细胞的生长。

Objective To investigate the effects of combined use of 5-aza-2′-deoxycytidine（5-AzadC）,trichostatin A（TSA）,5-fluorouracil（5-FU）and paclitaxel（PTX）on the growth of human gastric cancer cell line SGC-7901 and the expression of O6-methylguanine-DNA methyltransferase（MGMT）gene in vitro.Methods The cultured SGC-7901 cells were divided into eight groups of control,5-FU＋PTX,5-AzadC,TSA,5-AzadC＋TSA,5-AzadC＋5-FU＋PTX,TSA＋5-FU＋PTX and TSA＋5-AzadC＋5-FU＋PTX.Cell growth was evaluated by MTS and the expressions of MGMT mRNA and protein were detected by Western blot and RT-PCR,respectively.Results The growth of SGC-7901 cells was inhibited by 5-AzadC,TSA and 5-FU＋PTX in a time-dependent manner,which was more obvious in multi-drug groups than that in single-drug group（P〈0.05）.The expressions of MGMT mRNA and protein in SGC-7901 cells were higher in multi-drug groups than that in singledrug group in 72hours（P〈0.05）.Conclusion The growth of SGC-7901 cells is inhibited by combined use of 5-AzadC,TSA and 5-FU＋PTX through upregulating the expression of MGMT gene.