[摘要]：Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a main responder to intracellular hypoxia and is overexpressed in many human cancers, including renal cell carcinoma (RCC). To better understanding of the role of HIF-1 alpha in the tumorigenicity of RCC, we used short-hairpin RNA (shRNA) interference to inhibit HIF-1 alpha expression in the human renal cancer cell line, Caki-1 and OS-RC-2. Silencing of HIF-1 alpha significantly reduced the expression of HIF-1 alpha in both of renal cancer cell lines. In vitro downregulation of HIF-1 alpha inhibited Caki-1 and OS-RC-2 cell growth, migration and invasion. The results further showed that HIF-1 alpha silencing resulted in caspase-dependent apoptosis of Caki-1 and OS-RC-2 through regulation of PI3K/Akt pathway and Bcl-2-related proteins expression. In vivo animal studies showed that tumor growth was significantly inhibited in HIF-1 alpha shRNA-transfected RCC. Intratumor gene therapy with polyethylenimine-loaded HIF-1 alpha shRNA also resulted in tumor growth suppression. Thus, this study demonstrates that downregulation of HIF-1 alpha could suppress tumorigenicity of RCC through induction of apoptosis, and HIF-1 alpha shRNA may be a promising strategy for the treatment of RCC. Cancer Gene Therapy (2010) 17, 212-222; doi:10.1038/cgt.2009.66; published online 9 October 2009
