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目的研究洛伐他汀克服吉非替尼耐药与整合素β1、Survivin的相关性,并探讨其可能机制。方法将吉非替尼耐药的非小细胞肺癌(NSCLC)细胞株PC9分为4组:无药对照组(RPMI 1640培养液培养)、吉非替尼组(1μmol/L吉非替尼)、洛伐他汀组(5μmol/L洛伐他汀)和吉非替尼与洛伐他汀联合组(1μmol/L吉非替尼+5μmol/L洛伐他汀)。各组细胞分别用相应药物处理后,采用CCK-8法检测细胞的增殖抑制率,PCR法检测细胞中整合素β1、Survivin mRNA的表达水平,蛋白质印迹法检测整合素β1、Survivin蛋白的表达水平。结果与无药对照组、洛伐他汀组及吉非替尼组相比,洛伐他汀与吉非替尼联合组对吉非替尼耐药PC9细胞增殖的抑制作用增强(P<0.01),细胞中整合素β1、Survivin mRNA及蛋白的表达水平降低(P<0.01)。结论洛伐他汀联合吉非替尼克服吉非替尼耐药是通过阻断整合素β1-p-Akt-Survivin信号通路来实现的,有望成为克服吉非替尼耐药的一种有效策略。
Objective To investigate the relationship between lovastatin and gefitinib in the treatment of integrin β1 and Survivin and its possible mechanism. Methods Gefitinib-resistant non-small cell lung cancer (NSCLC) cell line PC9 was divided into four groups: drug-free control group (RPMI 1640 culture medium), gefitinib group (1μmol / L gefitinib) , Lovastatin group (5μmol / L lovastatin) and gefitinib combined with lovastatin (1μmol / L gefitinib + 5μmol / L lovastatin). After treatment with corresponding drugs, the cell proliferation inhibition rates were determined by CCK-8 assay. The expression of integrin β1 and Survivin mRNA was detected by PCR, and the expression of integrin β1 and Survivin protein were detected by Western blotting . Results Compared with the non-drug control group, the lovastatin group and the gefitinib group, the combination of lovastatin and gefitinib enhanced the inhibition of the proliferation of gefitinib-resistant PC9 cells (P <0.01) The expression of integrin β1, Survivin mRNA and protein were decreased (P <0.01). Conclusion Lovastatin combined with gefitinib can prevent gefitinib resistance by blocking the integrin β1-p-Akt-Survivin signaling pathway, which may be an effective strategy to overcome the resistance of gefitinib.