EGFR抑制剂吉非替尼对肝癌细胞增殖和凋亡的影响

Effect of EGFR inhibitor gefitinib on proliferation and apoptosis of hepatocellular carcinoma cells

目的探讨表皮生长因子受体(epidermalgrowthfactorreceptor,EGFR)抑制剂吉非替尼对人肝癌细胞株SMMC-7721增殖和凋亡的影响,为原发性肝癌的分子靶向治疗提供实验依据。方法应用免疫组化法检测SMMC-7721细胞中EGFR的表达,不同浓度吉非替尼处理SMMC-7721细胞48h后,MTT法检测细胞对该药物敏感性,流式细胞仪检测细胞凋亡变化。结果SMMC-7721细胞中EGFR呈强阳性表达,吉非替尼明显下调EGFR表达,抑制SMMC-7721细胞生长,呈剂量时间依赖性,8mmol/L吉非替尼组细胞凋亡率为(58·58±2·95)%,显著高于对照组(0·11±0·04)%,(P<0·01)。结论吉非替尼能够通过诱导细胞凋亡抑制SMMC-7721细胞生长,因而有望为肝癌的分子靶向治疗提供新的有效途径。

Objective To detect the effect of gefitinib, an inhibitor of epidermal growth factor receptor tyrosine kinase （EGFR-TK）,on the proliferation and apoptosis of human HCC SMMC-7721 cells, and to provide the evidence for potential molecular target therapy in the HCC clinical treatment. Methods The expression of EGFR were evaluated by immunohistochemical staining in HCC cells. After different concentration of gefitinib-treatment for 48 h, MTT method was used to detect the sensitivity of HCC SMMC-7721 cells to gefitinib. The human HCC cell lines SMMC-7721 was painted by AnnexinV-FITC/Propidium iodide（PI） and assayed its apoptotic rates by FCM. Results The expression of EGFR was positive intensively in human HCC cell line SMMC-7721. Gefitinib induced a dose and time-dependent apoptosis of the human HCC cell line SMMC-7721. The apoptosis rate of 8 mmol/L gefitinib group was （58.58 ± 2.95 ）%, significantly higher than control group （0. 11 ± 0. 04） %. Conclusion Gefitinib can inhibit the growth of human HCC cells by inducing cell apoptosis. Thus, EGFR-TK inhibition appears to be a promising novel approach for future treatment strategies of HCC.