目的研究组蛋白去乙酰化酶(HDACs)抑制剂西达本胺对胃癌细胞株体外抗增殖作用及其可能机制。方法用西达本胺终浓度为0、16、32、64、128、256μmol/L(分别为B、A1、A2、A3、A4、A5组)处理SGC-7901细胞24、48、72h。采用MTT法及流式细胞术分别检测细胞增殖及细胞凋亡,反转录PCR(RT-PCR)检测沉默信息调节因子2相关酶1(SIRT1)及HDAC11mRNA表达,实时荧光定量PCR(RT-qPCR)检测表皮生长因子受体(EGFR)mRNA表达,Western blot检测Notch1蛋白的表达。结果与B组相比,西达本胺呈浓度依赖性地抑制SGC-7901细胞增殖(P〈0.05),提高SGC-7901细胞凋亡率(P〈0.05),阻断SIRT1、HDAC11、EGFR mRNA以及Notch1蛋白表达(P〈0.05)。结论西达本胺可抑制SGC-7901细胞增殖,促进细胞凋亡;其作用机制可能是降低SIRT1、HDAC11基因的表达或与Notch及EGFR信号通路相关。
Objective To investigate the antiproliferative effect and underlying mechanism ofhistone deacetylase(HDAC) inhibitor chidamide on human gastric cancer cell line SGC-7901 in vitro. Methods SGC-7901 cells were divided into six groups of B (ehidamide 0 μmol/L), A1 (chidamide 16μmol/L), A2(ehidamide 32 μmol/L), Aa(chidamide 64 μmol/L), A4(ehidamide 128 μmol/L) and A5 (chidamide 256 μmol/L). The cell proliferation and cell apoptosis were detected by MTT and flowcytometry, respectively. The mRNA expressions of silent mating type information regulator 2 homolog 1(SIRT1) and HDACll were determined by reverse transcription-PCR(RT-PCR), and the mRNAexpression of epithelial growth factor receptor(EGFR) was measured by real-time quantitative-PCR (RT-qPCR). The protein expression of Notch1 was analyzed by Western blot. Results Comparedwith group B, chidamide inhibited cell proliferation and promoted cell apoptosis in a dose-dependent manner(P〈0. 05), and significantly blocked the expressions of SIRT1 mRNA, HDACll mRNA,EGFR mRNA and Notch1 protein (P〈0. 05 ). Conclusion Chidamide can inhibit SGC-7901 cell proliferation and enhance cell apoptosis probably via decreasing gene expressions of SIRT1 andHDAC11 or correlating with Notch and EGFR signaling pathway.