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目的:探讨新型过氧化物酶体增殖激活物受体(PPARγ)激动剂DH9对人肾癌细胞OS-RC-2的增殖抑制作用。方法:予以不同浓度的DH9及罗格列酮作用OS-RC-2细胞12 h、24 h和48 h,荧光素酶活性检测比较两种药物的PPARγ激动效应;MTT法检测细胞增殖情况;流式细胞术观察细胞周期;Annexin V-FITC/PI双染色流式细胞术测定细胞凋亡率;Western blot检测细胞内Bax及Bcl-2等蛋白的变化。结果:不同浓度的DH9与罗格列酮相比,对PPARγ的激动效应DH9明显低于罗格列酮,增殖抑制作用优于罗格列酮(P<0.05),并呈现明显的浓度、时间依赖性;加入PPARγ抑制剂GW9662前后DH9的增殖抑制作用差异无统计学意义(P>0.05);DH9作用细胞48小时后,G0/G1期细胞比例明显增加(P<0.05),S期细胞明显减少(P<0.05)。DH9可诱导细胞凋亡,伴随Bcl-2表达的减少以及Bax表达的增加。结论:OS-RC-2细胞中,DH9的增殖作用明显优于罗格列酮,且是通过PPARγ非依赖途径实现;DH9能将OS-RC-2细胞阻滞在G0/G1期,并通过影响Bcl-2和Bax蛋白表达促进细胞凋亡。
Objective: To investigate the inhibitory effect of novel peroxisome proliferator-activated receptor (PPARγ) agonist DH9 on human renal cell carcinoma cell line OS-RC-2. Methods: OS-RC-2 cells were treated with different concentrations of DH9 and rosiglitazone for 12 h, 24 h and 48 h, luciferase activity assay was used to compare the PPARγ agonism effect of two drugs; the proliferation of OS-RC-2 cells was detected by MTT assay; Cell cycle was observed by flow cytometry. Apoptosis rate was determined by flow cytometry with Annexin V-FITC / PI double staining. Western blot was used to detect the protein expression of Bax and Bcl-2. Results: Compared with rosiglitazone, different concentrations of DH9 had a significantly lower DH9 agonist effect on PPARγ than rosiglitazone, and its inhibitory effect on proliferation was better than that of rosiglitazone (P <0.05) (P> 0.05). After DH9-treated cells were treated with GW9662 for 48 hours, the proportion of cells in G0 / G1 phase was significantly increased (P <0.05), and the cells in S phase were significantly increased Decrease (P <0.05). DH9 induces apoptosis accompanied by a decrease in Bcl-2 expression and an increase in Bax expression. Conclusions: The proliferation of OS-RC-2 cells was significantly better than that of rosiglitazone and was mediated by PPARγ-independent pathway. DH9 blocked OS-RC-2 cells in G0 / G1 phase Affect the expression of Bcl-2 and Bax proteins and promote cell apoptosis.