恩度联合吉西他滨对肝癌HepG2细胞的抑制作用及对HIF-1α、VEGF表达的影响

The effect of endostar combined with gemcitabine on the inhibition and the expression of HIF-1α and VEGF of HepG2 cells

目的:探讨恩度(ES)、吉西他滨(GEM)单药及联合作用在体外对人肝癌细胞系HepG2细胞的增殖抑制和诱导凋亡作用,以及加药前后HIF-1α、VEGF表达的变化。方法:MTT比色法观察不同浓度恩度、吉西他滨及联合应用对HepG2细胞生长的抑制作用。采用流式细胞仪检测上述药物单独或联合应用对HepG2细胞凋亡率的影响。免疫组织化学技术检测上述药物单独或联合应用时HIF-1α、VEGF的表达差异。结果:恩度单药对HepG2细胞无明显增殖抑制及诱导细胞凋亡作用;吉西他滨单药及联合恩度对HepG2细胞有明显抑制作用,且均呈明显的剂量依赖关系,均可诱导细胞凋亡,联用时有协同作用(P<0.05)。加药组与空白组相比、联合用药组与单药组相比,HIF-1α、VEGF的表达水平均显著降低(P<0.05)。结论:吉西他滨单药以及与恩度联合能够抑制人肝癌HepG2细胞并诱导凋亡。两药联合有协同作用。其机制可能与HIF-1α、VEGF有关。

Objective：To observe the combination effects of endostar and gemcitabine in human hepatocellular carcinoma cell line HepG2 in vitro,and detect the expression of HIF-1α and VEGF after treatment with drugs.Methods：The experiment was divided into control group,endostar group,gemcitabine group,and endostar ＋ gemcitabine group.Cell growth inhibition was assessed by MTT and apoptosis was observed by flow cytometry.The expression of HIF-1α,VEGF was detected by immunohistochemical method.Results：Single endostar could not inhibit proliferation and induce apoptosis of human hepatocellular carcinoma cell line HepG2 cells.But single gemcitabine and combined treatment could markably inhibit proliferation of human hepatocellular carcinoma cell line HepG2 cells in dose-dependent response.Also can induce apoptosis.Combined application can enhance apoptosis（P 0.05）.The expression of HIF-1α and VEGF was down-regulated when combined treatment（P 0.05）.Conclusion：Gemcitabine has the effect of inhibition on the proliferation and induction of apoptosis in human hepatocellular carcinoma cell line HepG2 cells.Combining use can enhance apoptosis.The apoptosis was related to down-related of HIF-1α and VEGF.