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学科主题: 临床医学
题名:
Peroxisome proliferator-activated receptor gamma ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines
作者: Yang, FG; Zhang, ZW; Xin, DQ; Shi, CJ; Wu, JP; Guo, YL; Guan, YF
关键词: renal cell carcinoma ; peroxisorne proliferator-activated receptor gamma ; cell cycle ; apoptosis ; cyclin ; cdk
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2005-06-01
DOI: 10.1111/j.1745.7254.2005.00103.x
卷: 26, 期:6, 页:753-761
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: PPAR-GAMMA ; CANCER CELLS ; PITUITARY-ADENOMAS ; SIGNALING PATHWAYS ; GROWTH-INHIBITION ; GENE-EXPRESSION ; PROSTATE-CANCER ; RETINOIC ACID ; TROGLITAZONE ; DIFFERENTIATION
英文摘要:

Aim: To study the effect of peroxisome proliferator-actived receptor gamma (PPAR gamma) ligands on cell proliferation and apoptosis in human renal carcinoma cell lines.

Methods: The expression of PPAR gamma was investigated by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. The effect of thiazolidinedione (TZD) PPAR gamma ligands on growth of renal cell carcinoma (RCC) cells was measured by MTT assay and flow cytometric analysis. Cell death ELISA, Hoechst 33342 fluorescent staining and DNA ladder assay were used to observe the effects of PPAR gamma ligands on apoptosis. Regulatory proteins of cell cycle and apoptosis were detected by Western blot analysis.

Results: PPAR gamma was expressed at much higher levels in renal tumors than in the normal kidney (2.16 +/- 0.85 vs 0.90 +/- 0.73; P < 0.01). TZD PPAR gamma ligands inhibited RCC cell growth in a dose-dependent manner with IC50 values of 7.08 mu mol/L and 11.32 mu mol/L for pioglitazone, and 5.71 mu mol/L and 8.38 mu mol/L for troglitazone in 786-O and A498 cells, respectively. Cell cycle analysis showed a G(0)/G(1) arrest in human RCC cells following 24-h exposure to TZD. Analysis of cell cycle regulatory proteins revealed that TZD decreased the protein levels of proliferating cell nuclear antigen, pRb, cyclin D-1, and Cdk4 but increased the levels of p21 and p27 in a time-dependent manner. Furthermore, high doses of TZD induced massive apoptosis in renal cancer cells, with increased Bax expression and decreased Bcl-2 expression.

Conclusion: TZD PPAR gamma ligands showed potent inhibitory effect on proliferation, and could induce apoptosis in RCC cells. These results suggest that ligands for PPAR gamma have potential antitumor effects on renal carcinoma cells.

语种: 英语
WOS记录号: WOS:000229917700016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56016
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Inst Urol, Dept Mol Biol, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100034, Peoples R China

Recommended Citation:
Yang, FG,Zhang, ZW,Xin, DQ,et al. Peroxisome proliferator-activated receptor gamma ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines[J]. ACTA PHARMACOLOGICA SINICA,2005,26(6):753-761.
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