Gefitinib对人结肠癌Caco-2细胞增殖与凋亡的影响

Effect of gefitinib on proliferation and apoptosis of human colon carcinoma Caco-2 cells

目的探讨Gefitinib对人结肠癌Caco-2细胞增殖与凋亡的影响。方法2.5~30μmol/L Gefitinib处理Caco-2细胞24~72 h,MTS、流式细胞术、免疫荧光、Western blot检测细胞增殖、凋亡、线粒体膜电位、MAPK及凋亡相关蛋白表达。结果Gefitinib呈浓度和时间依赖性抑制Caco-2细胞增殖(P<0.01),诱导细胞凋亡,降低线粒体膜电位(P<0.05)。Gefitinib浓度依赖性上调p-p38、p-JNK、Cleaved-PARP蛋白表达,下调p-ERK、Caspase-3表达(P<0.01)。结论Gefitinib通过调节Caco-2细胞中MAPK磷酸化蛋白和Caspase-3蛋白表达,从而诱导线粒体膜电位降低,促进细胞凋亡。

Objective To study the effect of gefitinib on proliferation and apoptosis of human colon carcinoma Caco-2 cells.Methods Caco-2 cells were treated with 2.5-30μmol/L gefitinib for 24-72 h.Cell proliferation,apoptosis,mitochondrial membrane potential,and expression of mitogen activated protein kinase(MAPK)and apoptosis related proteins were evaluated by MTS,flow cytometry,immunofluorescence and Western blot,respectively.Results Gefitinib inhibited proliferation(P<0.01),induced apoptosis,and decreased mitochondrial membrane potential(P<0.05)of Caco-2 cells in a concentration and time-dependent manner.Gefitinib up-regulated expression of p-p38,p-JNK and cleaved PARP and downregulated expression of p-ERK and caspase-3 in a dose-dependent manner(P<0.01).Conclusion Gefitinib could promote apoptosis of Caco-2 cells via regulation of MAPK phosphorylation and caspase-3 expression and reduction of mitochondrial membrane potential.