【摘要】 背景:骆驼蓬碱可通过下调环氧合酶-2(COX-2)表达抑制胃癌细胞增殖,但其分子机制尚未完全明确。目的:研究骆驼蓬碱对胃癌细胞增殖、凋亡的影响,探讨PTEN/Akt/MDM2信号通路在该过程中的作用。方法:以不同浓度(2、4、8、16、32μg/m L)骆驼蓬碱干预人胃腺癌细胞株SGC-7901和MKN-45 24 h、48 h和72 h,分别采用MTT法和Hoechst染色检测细胞增殖和凋亡情况;蛋白质印迹法检测PTEN、COX-2表达以及Akt、MDM2磷酸化水平。结果:骆驼蓬碱呈剂量和时间依赖性地抑制SGC-7901、MKN-45细胞增殖,并诱导其发生典型的凋亡形态学改变。骆驼蓬碱呈剂量依赖性地上调PTEN表达、抑制Akt、MDM2磷酸化以及COX-2表达。结论:骆驼蓬碱可能通过PTEN/Akt/MDM2信号通路下调COX-2表达,抑制胃癌细胞增殖并诱导其凋亡。更多还原

【Abstract】 Background: Previous study has found that harmine inhibited the proliferation of gastric cancer cells by downregulating cyclooxygenase-2(COX-2) expression. However,its molecular mechanism is not fully clear. Aims: To investigate the effect of harmine on proliferation and apoptosis of gastric cancer cells,and explore the role of PTEN/Akt/MDM2 signaling pathway in this process. Methods: Human gastric adenocarcinoma cell line SGC-7901 and MKN-45 were treated with harmine at different concentrations(2,4,8,16,32 μg/m L) for 24,48,and 72 hours. The cell proliferation and apoptosis were detected by MTT assay and Hoechst staining,respectively. The expressions of PTEN,COX-2,phosphorylated Akt(p-Akt) and p-MDM2 were measured by Western blotting. Results: Harmine dose-and timedependently inhibited proliferation and induced apoptosis of SGC-7901 and MKN-45 cells. Also,harmine dose-dependently increased PTEN expression,and inhibited p-Akt,p-MDM2 and COX-2 expressions in SGC-7901 and MKN-45 cells.Conclusions: Harmine may inhibit proliferation and induce apoptosis of gastric cancer cells via down-regulating COX-2 expression through PTEN/Akt/MDM2 signaling pathway.更多还原