[Peroxisome proliferator-actived receptor-gamma ligand troglitazone induces apoptosis in renal cell carcinoma]
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Published on: August 23, 2024
Feng-guang Yang1, Zhi-wen Zhang, Dian-qi Xin
1Department of Urology, Peking University First Hospital, Beijing 100034,China.
Unlabelled:
OBJECTIVE To investigate the expression of peroxisome proliferator-actived receptor-gamma (PPAR-gamma)and the inducement of apoptosis by PPAR-gamma ligand in renal cell carcinoma(RCC)-derived cell lines.
Methods:
RT-PCR and Western blot analysis were performed to determined the expression of PPAR-gamma mRNA and protein in two RCC derived cell lines(786-O and A498) and two normal kidney(NK)-derived cell lines(HK-2 and HMCC). Two RCC cell lines were treated with 50 micromol/L troglitazoned for and evaluated for the effects of antidiabetic thiazolidinediones (TZDs) on the cells apoptosis by fluorescence microscopy and DNA ladder assay. The mutative expressions of Bcl-2 and Bax before and after TZDs treatment were also performed by western blot analysis.
Results:
The expression of PPAR-gamma was observed to be stronger in 786-O and A498 cells than in HK-2 and HMCC cells by RT- PCR and Western blot analysis. Treated with 50 micromol/L troglitazone (for 48 h) it induced typical apoatosis in 786-O and A498 cells. After treatment, a decrease in Bcl-2 expression in RCC cells was observed by Western blot analysis,and the expression of Bax,however,was up-regulated.
Conclusion:
The results reveal that troglitazone has the tumor-suppressive effect on RCC cells. High-affinity PPAR-gamma ligands (TZDs) may be the candidates for a novel approach to the treatment of this refractory neoplasm.
Insights
Troglitazone, a PPAR-gamma ligand, demonstrated tumor-suppressive effects in renal cell carcinoma (RCC) by inducing apoptosis. This suggests thiazolidinediones (TZDs) could be a novel treatment for RCC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) is a significant health concern with limited treatment options.
- Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor with potential roles in cancer.
- Understanding PPAR-gamma's role in RCC is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate PPAR-gamma expression in RCC cell lines.
- To determine the effect of PPAR-gamma ligands on apoptosis in RCC cells.
- To explore the potential of PPAR-gamma ligands as a novel RCC treatment.
Main Methods:
- Gene and protein expression analysis of PPAR-gamma using RT-PCR and Western blot in RCC and normal kidney cell lines.
- Induction of apoptosis in RCC cells treated with troglitazone (a PPAR-gamma ligand).
- Assessment of apoptosis via fluorescence microscopy and DNA ladder assay, with analysis of Bcl-2 and Bax expression.
Main Results:
- PPAR-gamma expression was significantly higher in RCC cell lines (786-O, A498) compared to normal kidney cells (HK-2, HMCC).
- Troglitazone treatment induced apoptosis in RCC cells.
- Troglitazone altered the expression of apoptosis-related proteins, decreasing Bcl-2 and increasing Bax.
Conclusions:
- Troglitazone exhibits a tumor-suppressive effect on renal cell carcinoma.
- High-affinity PPAR-gamma ligands, such as thiazolidinediones (TZDs), represent a promising avenue for novel RCC therapies.
- Further research into TZDs could lead to effective treatments for this challenging neoplasm.
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