Effect of HIF1? and HIF2? on human renal cell carcinoma and their mechanisms: an RNAi approach comparison
- VernacularTitle:RNA干扰对比观察HIF1?和HIF2?在人肾癌细胞中的作用及机制
- Author:
Li WANG
;
Suxia WANG
;
Changlin MEI
- Publication Type:Journal Article
- Keywords:
hypoxia-inducible factor;
kidney neoplasms;
apoptosis;
RNA interference
- From:
Academic Journal of Second Military Medical University
1985;0(06):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate and compare the effect and the possible mechanisms of 2 hypoxia-inducible factors(HIF) 1? and 2? on renal cell carcinoma(RCC) by RNA interference(RNAi) method.Methods: Chemically synthesized HIF-1? and HIF-2? RNAi were transfected into RCC cell line A498 by liposome transient transfection.Normal proximal tubule cell line HK-2 and A498 were separately treated with medium and liposome as controls.The expressions of VEGF,ET-1,bcl-2 and Ki67 were observed by RT-PCR or Western blot 24 h after RNAi.Cell apoptosis was detected by flow cytometry and fluorescence microscopy.Results: Expressions of HIF-1? and HIF-2? RNAi were higher in A498 than those in HK-2,and the 2 genes were successfully blocked after RNAi.HIF-1? RNAi resulted in a significant decrease of ET-1,bcl-2 and Ki67 expression,with increased apoptosis and necrosis of cells.HIF-2? RNAi only resulted in a decrease of VEGF.Conclusion: Both HIF-1? and HIF-2? play important roles in regulation of angiogenesis; moreover,HIF-1? might also regulate proliferation of tumor cells,possibly through regulating anti-apoptotic genes.It is implied the existance of different transcription regulation functions and gene combining sites between HIF-1? and HIF-2?.
