羧酸类化合物DJ5对人肾囊肿衬里上皮细胞的增殖抑制作用  

Anti-proliferative Effect of Carboxylic Acid Compounds DJ5 on Autosomal Dominant Polycystic Kidney Disease Cystic Lining Epithelial Cells

作　　者：王文苓[1] 苏晓峰[1] 付莉莉[1] 梅长林[1] 

机构地区：[1]第二军医大学附属长征医院,上海200003

出　　处：《中国中西医结合肾病杂志》2012年第12期1053-1057,共5页Chinese Journal of Integrated Traditional and Western Nephrology

摘　　要：目的:观察羧酸类化合物DJ5对人肾囊肿衬里上皮细胞WT9-12的增殖抑制作用并探讨其作用机制。方法:MTT法检测细胞增殖,LDH释放实验检测细胞毒性,流式细胞术检测细胞周期和细胞凋亡,Western blot检测周期相关蛋白P21、cyclinA,凋亡蛋白PARP,通路蛋白Akt、FoxO3a蛋白表达。结果:实验表明100μmol/L的DJ5作用WT9-12细胞72h,细胞增殖抑制率为59.2%,DJ5使细胞周期阻滞在S期并促进细胞早期凋亡。DJ5可上调WT9-12细胞周期抑制蛋白P21表达、下调cyclinA表达;使PARP活性片段89kD表达明显增加。DJ5可下调磷酸化Akt、磷酸化FoxO3a表达、上调FoxO3a表达。结论:DJ5通过阻滞细胞周期、促进细胞凋亡及抑制Akt-FoxO3a通路蛋白发挥抑制WT9-12细胞增殖作用。Objective：To observe the anti - proliferative effect of Carboxylic Acid Compounds DJ5 on autosomal dominant polycystic kidney disease cystic lining epithelial cells and to investigate the underlying molecular mechanism. Methods： ADPKD cystic lining epithelial （WT9 - 12） cells were stimulated by DJ5 with different concentrations. After treatment, MTY method was porformed to detect the level of proliferation, LDH release method was performed to detect the cytotoxicity ;flow cytometry was used to determine the cell cycle distribution and the apoptosis rate, western blotting was used to detect the protein expressions of P21, cyclin A, PARP, Akt, phosphorylated Akt, FoxO3a, phosphorylated FoxO3a. Results：Treatment of WT9 -12 cells with DJ5 resulted in a time- de pendent and dose - dependent inhibition of cell proliferation. Treatment of WT9 - 12 cells with DJ5 100 μmol/L for 72 h, the inhibi ton rate was 59.2%. DJ5 can make WT9 - 12 cells accumulated in S phase , up - regulate the expression of P21 CIP/WAF1 and down regulate cyclin A. DJ5 100 trmol/L can make WT9 - 12 apoptosis, and the expression of PARP with 89kd is enhanced. Phos phorylated Akt, phosphorylated FoxO3a is down -regulation and FoxO3a is up - regulation in DJ5 groups. Condusion：DJ5 inhibits the proliferation of WT9 -12 cells through accumulating WT9 -12 cells in S phase, promoting apoptosis and regulat!ng Akt -FoxO3a signal pathway.

关 键 词：DJ5常染色体显性多囊肾病羧酸类化合物 肾囊肿衬里上皮细胞 

分 类 号：R965[医药卫生—药理学]