cGMP依赖性蛋白激酶抑制肺癌A549/DDP细胞株的顺铂耐药性

c GMP-dependent protein kinases inhibit cisplatin resistance of lung cancer cell line A549 / DDP

目的:观察Ⅰα亚型c GMP依赖性蛋白激酶(c GMP-dependent protein kinaseⅠα,PKGⅠα)和Ⅱ型c GMP依赖性蛋白激酶(PKGⅡ)对肺癌细胞顺铂耐药的影响。方法:用编码PKGⅠα和PKGⅡc DNA的腺病毒载体感染A549/DDP细胞,使其高表达PKGⅠα和PKGⅡ并以相应激活剂激活,用CCK8试剂盒检测顺铂作用后肺癌细胞的增殖活性,蛋白质印迹法检测PKGs对A549/DDP细胞多药耐药性蛋白1(multidrug resistance protein 1,MRP1)和肺耐药相关蛋白(lung resistance related protein,LRP)表达的影响。结果:PKGⅠα和PKGⅡ表达增高并被激活后,均可加强顺铂对A549/DDP细胞增殖的抑制,并明显降低A549/DDP细胞MRP1和LRP的表达。结论:PKGⅠα和PKGⅡ可通过降低耐药相关蛋白MRP1和LRP的表达,抑制A549/DDP细胞的耐药活性,发挥抗癌作用。

Objective:To investigate the effects of PKGⅠαand PKGⅡ on cisplatin resistance of drug-resistant lung cancer cell line A549 /DDP.Methods:A549 /DDP cells were infected with adenoviral vector encoding cDNA of PKGⅠαand PKGⅡ and the kinases were activated by respective activator.CCK8 kit was used to detect the proliferation of the cells.Western blotting was applied to detect the influence of PKGⅠαand PKGⅡ on the expression of drug resistance-related proteins,including multidrug resistance protein 1 (MRP1)and lung resistance related protein (LRP).Results:When the expression and activity were in-creased,both PKGⅠαand PKGⅡ could increase the inhibitory effect of cisplatin on proliferation of A549 /DDP cells.The expression of MRP1 and LRP was inhibited by both PKGⅠαand PKGⅡ.Conclusion:PKGⅠαand PKGⅡ could inhibit the cisplatin resistant activity through decreasing the expression of drug resistance-related protein MRP1 and LRP.