冬凌草甲素逆转人胃癌细胞SGC 7901/DDP顺铂耐药的作用及机制研究

Oridonin Induces Apoptosis and Reverses Drug Resistance in Cisplatin Resistant Human Gastric Cancer Cells

目的:探讨天然化合物冬凌草甲素(oridonin,Ori)对顺铂(cisplatin,DDP)耐药的胃癌细胞SGC7901/DDP的耐药逆转作用及其相关机制。方法:MTT法检测Ori对SGC7901/DDP的毒性作用及与DDP的协同作用;台盼蓝计数实验及集落形成实验检测Ori对细胞生长的抑制作用;核染色免疫荧光及免疫印迹法检测Ori诱导细胞凋亡作用及逆转SGC7901/DDP细胞DDP耐药的作用机理。结果:Ori能显著抑制SGC7901/DDP细胞增殖、生长和集落形成,并诱导凋亡。机制研究发现,Ori显著抑制与肿瘤多药耐药相关的蛋白的表达,包括P-糖蛋白(P-glycoprotein)、多药耐药性相关蛋白(multidrug resistance-associated protein 1,MRP1)和细胞周期蛋白Cyclin D1;另外,Ori还可以诱导磷酸酶2A的癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)表达下调,Akt磷酸化下调。结论:Ori能够逆转SGC7901/DDP对DDP耐药并诱导凋亡,其机制可能是通过下调多药耐药蛋白P-gp、MRP1及抑制CIP2A/Akt信号级联。

Objective To explore the effects of natural compound oridonin on inducing apoptOsis and reversing drug resistance of cisplatin （DDP） resistant human gastric cancer cells and its possible mechanisms.Methods MTT method was used to detect the inhibitory effects and synergistic effect with DDP of oridonin in DDP-resistant human gastric cancer SGC7901/ DDP cells.Trypanblau counting and colony formation trials were used to detect the inhibitory effects of oridonin on the growth of SGC7901/DDP cells.DAPI staining and Western blot were used to investigate the mechanisms Of oridonin on re- versing multi-drug resistance of SGC7901/DDP cells. Results Oridonin obviously inhibited the proliferation, growth and colony formation of SGC7901/DDP Cells and induced the apoptosis.The results also demonstrated that oridonin obviously inhibited the expression of multidrug resistance correlated proteins, including P-glycoprotein, multidrug resistance-associated protein 1 （ MRP1 ） and cyclin D1.Moreover, oridouin could also down regulated the expressions of cancerous inhibitor of protein phosphatase 2A（CIP2A） and the phosphorylation of Akt.Conclusion Oridonin could reverse the multi-drug resistance and induce apotosis of SGC7901/DDP ,which may carry out through down-regulating the expression of P-gp, MRP1 and inhibiting the cascade connection of CIP2A/Akt.