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Peroxisome proliferator-activated receptor gamma ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines
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
2005-06-01
DOI10.1111/j.1745.7254.2005.00103.x
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
引用统计
被引频次:60[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56016
专题北京大学第一临床医学院_泌尿外科
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
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GB/T 7714
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.
APA Yang, FG.,Zhang, ZW.,Xin, DQ.,Shi, CJ.,Wu, JP.,...&Guan, YF.(2005).Peroxisome proliferator-activated receptor gamma ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines.ACTA PHARMACOLOGICA SINICA,26(6),753-761.
MLA Yang, FG,et al."Peroxisome proliferator-activated receptor gamma ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines".ACTA PHARMACOLOGICA SINICA 26.6(2005):753-761.
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