吉非替尼对子宫内膜癌Ishikawa细胞增殖和凋亡的影响

目的:探讨EGFR酪氨酸激酶抑制剂吉非替尼(Gefitinib)对子宫内膜癌Ishikawa细胞增殖和凋亡的影响,并探讨其内在作用机制。方法:MTT法检测不同浓度吉非替尼作用后细胞的增殖抑制率。采用流式细胞术检测吉非替尼作用48h后的细胞凋亡率及细胞周期分布,并用倒置显微镜对细胞进行形态学观察。Western blot法检测不同浓度吉非替尼作用细胞48h后细胞内p-Akt、CyclinD1蛋白水平表达的变化。结果:吉非替尼能显著抑制Ishikawa细胞的增殖,促进细胞凋亡,且呈时间-剂量依赖性(P0.05),并使细胞周期中G0/G1期比例升高(P0.05),而对S期和G2/M期比例无明显影响(P0.05)。吉非替尼作用48h后,Ishikawa细胞中p-Akt、CyclinD1蛋白表达随着吉非替尼浓度的增加逐渐下降(P0.05)。结论:吉非替尼对人子宫内膜癌细胞Ishikawa的体外生长具有明显的抑制作用,并能诱导Ishikawa的凋亡,导致G0/G1期细胞阻滞,其分子机制可能与吉非替尼下调p-Akt蛋白及CyclinD1蛋白的表达有关。

Effect of gefitinib on the proliferation and apoptosis to human endometrial cancer cell Ishikawa

Objective:To study the effect and mechanism of gefitinib(EGFR tyrosine kinase inhibitor) on the proliferation and apoptosis in human endometrial carcinoma cell line Ishikawa.Methods:MTT method was used to detect cell proliferation after Ishikawa cells treated by gefitinib.Flow cytometry was used to detect cell apoptosis,cell cycle and the morphology of the cells was observed by inverted microscope.Western blot was used to detect the influence of different concentrations of gefitinib to the p-Akt and CyclinD1 protein expression in Ishikawa cells.Results:Gefitinib inhibited cell proliferation of Ishikawa cells and induced apoptosis with different concentration,by a dose and time-dependent manner(P < 0.05).And gefitinib increased the proportion of G0/ G1phase cells(P < 0.05),but it had no significant effect on the proportion of S and G2/ M phase cells(P > 0.05).After treated by gefitinib for 48 hours,the expressions of p-Akt and CyclinD1 were decreased in a concentration-dependent manner(P < 0.05).Conclusion:Gefitinib significantly inhibits the proliferation of human endometrial carcinoma Ishikawa cells in vitro,induces cell apoptosis and blocks the cell cycle at G0/ G1phase.The molecular mechanism may be related to down-regulated expression of p-Akt and CyclinD1 protein.