于飞 龙集智 刘晓玲 韩博 莫峥 熊锡山 王汉斌.一种新型PPARr激动剂对人肾癌细胞增殖抑制的实验研究[J].,2015,15(15):2851-2854 |
一种新型PPARr激动剂对人肾癌细胞增殖抑制的实验研究 |
Effects of a Novel PPARr Agonist on Cell Proliferation in OS-RC-2 Cellsin Vivo |
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DOI: |
中文关键词: 肾细胞癌 PPARr受体激动剂 细胞增殖 凋亡 |
英文关键词: Human renal carcinoma Peroxisome proliferator-activated receptor ragonist Proliferation Apoptosis |
基金项目:国家自然科学基金青年基金项目(H1609) |
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中文摘要: |
目的:探讨新型过氧化物酶体增殖激活物受体(PPARr)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PPARr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;AnnexinV-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PPARr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PPARr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
PPARr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。 |
英文摘要: |
Objective:To investigate the anti-tumor effect of peroxisome proliferator-activated receptor r(PPARr) 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 (1-100 uM,) for 12, 24, and 48 h. The PPARragonistic 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 PPARr agonistic activity
of DH9 was much lower than rosiglitazone (P<0.05). The proliferation inhibition rate was not impaired by a PPARr inhibitor,
GW9662, suggesting that DH9 inhibited the proliferation in a PPARr-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.Conclusion:DH9 can more effectively block the proliferation of the OS-RC-2 cell line independent of PPARr. The effects
may be related to the arrest of G0/G1 phase and induction of apoptosis. |
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