Objective To study the antitumor activity of high-dose pulsatile gefitinib administration on non-small cell lung cancer PC9/GR cell and its potential mechanisms. Methods The proliferation inhibitory effect of different concentrations of gefitinib on PC9/GR cells was measured with MTT assay and the value of IC50 was calculated. Ac-cording to IC50 value, we divided the experiment into the routine gefitinib administration group and gefitinib high dose pulsatile administration group on PC9/GR cell. The cell apoptosis morphological change was detected by the fluorescent microscope. The flow cytometry was used to analyze the alteration of cell apoptosis rate. ERFR signal related protein such as p-EGFR, EGFR, p-AKT, AKT, p-ERK and ERK were measured using Western blot. Re-sults Compared with the control group, the apoptosis rates were markedly increased when treated with high dose pulsatile gefitinib(P<0. 01). Western blot results showed that, compared with the control group, gefitinib clearly decreased the expressions of p-EGFR, p-AKT, p-ERK when treated with high dose pulsatile gefitinib(P<0. 05). Conclusion High-dose pulsatile gefitinib can significantly inhibit the cell proliferation and induce cell apoptosis. The mechanism of antitumor effect may be due to the mutual interference with the EGFR signaling pathway.%目的：探讨吉非替尼高剂量脉冲式给药作用于非小细胞肺癌吉非替尼耐药细胞株PC9/GR的抗肿瘤效应及其可能机制。方法 MTT法检测吉非替尼对PC9/GR的增殖抑制率,计算半数抑制浓度( IC50),根据IC50值,分为吉非替尼常规剂量给药组和脉冲式剂量给药组,分别作用于PC9/GR细胞株,荧光显微镜观察各处理组中细胞凋亡形态学变化,流式细胞术检测细胞凋亡率,Western blot法检测表皮生长因子受体( EGFR)相关信号通路蛋白如p-EGFR、EGFR、磷酸化的丝氨酸/苏氨酸蛋白激酶( p-AKT)、AKT、磷酸化的细胞外调节蛋白激酶( p-ERK)、ERK表达水平。结果与对照组比较,高剂量脉冲式给药组细胞凋亡率明显增加(P <0．01),同时可明显下调p-EGFR、p-ERK、p-AKT蛋白表达(P<0．05)。结论吉非替尼高剂量脉冲式给药在一定程度上可以显著抑制PC9/GR细胞增殖,促进细胞凋亡,机制可能与阻断EGFR信号通路传导有关。
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