摘要
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 anti-tumor effect ofperoxisome proliferator-activated receptor γ（PPARγ） ligand DH9 on the proliferation of human renal carcinoma cell line OS-RC-2. Methods： Human renal carcinoma cell line OS-RC-2 was treated with DH9 and rosiglitazone （ROS） in various concentrations （1-100μM,） for 12, 24, and 48 h. The PPARγagonistic activity by DH9 and ROS was compared by Transfection and Luciferase Assay. The inhibition rate was assessed by MTT. Cell cycle and cell apoptosis were determined by flow cytometry. The expression of Bax and Bcl-2 were detected by Western blot. Results： The proliferation of renal cell carcinoma OS-RC-2 cells was effectively inhibited by DH9 in a concentration-dependent and time-dependent manner. It was noted that the efficiency of cell growth inhibition by DH9 was much more potent than rosiglitazone （P〈0.05）, although the PPARγ agonistic activity of DH9 was much lower than rosiglitazone （P〈0.05）. The proliferation inhibition rate was not impaired by a PPARγ inhibitor, GW9662, suggesting that DH9 inhibited the proliferation in a PPARγ-independent manner. Cell cycle phase analysis revealed a decreased proportion of S phase, with arrest at G0/G1 in this process（P〈0.05）. Additionally, DH9 could induce apoptosis through Bcl-2/Bax pathway. Conclusions： DH9 can more effectively block the proliferation of the OS-RC-2 cell line independent of PPARγ. The effects may be related to the arrest of G0/G1 phase and induction of apoptosis.
出处
《现代生物医学进展》
CAS
2015年第15期2851-2854,2862,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金青年基金项目(H1609)
关键词
肾细胞癌
PPARγ受体激动剂
细胞增殖
凋亡
Human renal carcinoma
Peroxisome proliferator-activated receptor γ agonist
Proliferation
Apoptosis
