吉非替尼与紫杉醇联合对卵巢癌细胞凋亡影响的观察

Effect of gefitinib combined with paelitaxel on apoptosis of ovarian cancer cell line HO8910

目的:探讨吉非替尼联合紫杉醇诱导人卵巢癌细胞凋亡的影响。方法:吉非替尼单独或联合紫杉醇作用卵巢癌HO8910细胞,以蛋白质印迹法检测EGFR下游信号磷酸化Akt(p-Akt)、磷酸化细胞外信号调节激酶(p-ERK)和细胞核增殖抗原(PCNA),以MTT法检测细胞增殖率,FCM法检测细胞周期分布和凋亡。结果:吉非替尼单用在0.25～4.00μmol/L浓度范围内呈浓度依赖性抑制卵巢癌HO8910细胞增殖,1.0μmol/L浓度单独作用24h则细胞周期主要分布于G1期,p-Akt、p-ERK和PCNA蛋白水平下降,72h时细胞凋亡增加,与对照组比较,差异均有统计学意义,P<0.05。吉非替尼与紫杉醇合用不仅能更显著的抑制细胞增殖,而且凋亡细胞显著增加(P<0.05),与对应浓度单用紫杉醇比较,差异均有统计学意义,P<0.05。结论:吉非替尼与紫杉醇合用能显著抑制卵巢癌HO8910细胞增殖、诱导凋亡,两种药物合用具有协同作用。

OBJECTIVE： To observe the effect of gefitinib combined with paelitaxel on proliferatio of human ovarian cancer cell line HO8910,and to discuss its possible mechanism.METHODS： Ovarian cancer cells were treated with EGFR inhibitor gefitinib alone or in combination with paelitaxel.Western blot analysis was used to assess the activation of the common downstream signals of Akt,ERK,and PCNA（Proliferating Cell Nuclear Antigen）.MTT assay was used to determine the cell proliferation rate.FCM for cell cycle phases and apoptosis.RESULTS： From 0.25 to 4.00 μmol/L concentratin,gefitinib alone inhibited proliferation of cells HO8910 at dose-dependence,and the cycle of cells treated gefitinib（1.0 μmol/L） was main G1 phase,and level of p-Akt,p-ERK,and PCNA proteins decreased significantly at 24 h,and cell apoptosis increased at 72 h,compared with control（P0.05）.A combination of gefitinib and paelitaxel resulted in significant decreases in cell proliferation in HO8910 cells,and further induced cell apoptosis,compared with paelitaxel alone.CONCLUSIONS： Gefitinib can suppress the EGFR downstream signaling activation,and enhanced responses of ovarian cancer cells to paelitaxel.The combination treatment produced synergistic inhibition.