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目的:研究联合洛伐他汀(lovastatin)和吉非替尼(gefi tinib)对体外诱导吉非替尼获得性耐药的非小细胞肺癌细胞株PC9细胞凋亡以及相关蛋白表达的影响,并探讨其可能的机制。方法:应用洛伐他汀联合吉非替尼处理耐吉非替尼的非小细胞肺癌PC9细胞株后,采用WST-1法检测不同药物处理对PC9细胞增殖的影响,Hoechst33342荧光染色法观察细胞凋亡形态,FCM法观察细胞凋亡状况,蛋白质印迹法检测凋亡相关蛋白的表达水平。结果:洛伐他汀联合吉非替尼可在体外诱导耐吉非替尼的PC9细胞凋亡,抑制其细胞增殖;洛伐他汀联合吉非替尼可诱导耐吉非替尼的PC9细胞中磷酸化表皮生长因子受体(phosphorylated epidermal growth factor receptor,p-EGFR)、磷酸化蛋白激酶B(phosphorylated protein kinase B,p-AKT)和磷酸化细胞外调节蛋白激酶1/2(phosphorylated extracellular signal-regulated kinase1/2,p-ERK1/2)蛋白表达水平明显下调。结论:在体外诱导吉非替尼获得性耐药的非小细胞肺癌细胞株PC9中,洛伐他汀可以克服吉非替尼耐药,两者具有良好的协同作用,提示两药联合对于出现吉非替尼耐药的非小细胞肺癌的临床治疗可能具有很大的应用潜力。
AIM: To investigate the effects of lovastatin and gefi tinib on the apoptosis and related protein expression of gefitinib-resistant non-small cell lung cancer cell line PC9 induced in vitro Its possible mechanism. Methods: The PC9 cells were treated with lovastatin and gefitinib in non-small cell lung cancer. WST-1 method was used to detect the effect of different drugs on the proliferation of PC9 cells. Hoechst33342 staining was used to observe the apoptosis of PC9 cells. The morphology of apoptotic cells was observed by FCM. The expression of apoptosis-related proteins was detected by Western blotting. Results: Lovastatin combined with gefitinib could induce the apoptosis of PC9 cells resistant to gefitinib in vitro and inhibited the proliferation of PC9 cells. Lovastatin combined with gefitinib could induce the phosphorylation of phosphoric acid The expression of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase1 / 2, p-ERK1 / 2) protein expression was significantly down-regulated. CONCLUSION: Lovastatin can overcome gefitinib resistance in PC9 cells with induced resistance to gefitinib in vitro. The two have good synergistic effects, suggesting that the combination of two drugs for the occurrence of gefitinib The clinical management of non-tinidin resistant non-small cell lung cancer may have great potential for use.