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Silencing of HIF-1α suppresses tumorigenicity of renal cell carcinoma through induction of apoptosis

Cancer Gene Therapy volume 17, pages 212–222 (2010)Cite this article

Abstract

Hypoxia-inducible factor-1α (HIF-1α) 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-1α in the tumorigenicity of RCC, we used short-hairpin RNA (shRNA) interference to inhibit HIF-1α expression in the human renal cancer cell line, Caki-1 and OS-RC-2. Silencing of HIF-1α significantly reduced the expression of HIF-1α in both of renal cancer cell lines. In vitro downregulation of HIF-1α inhibited Caki-1 and OS-RC-2 cell growth, migration and invasion. The results further showed that HIF-1α 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-1α shRNA-transfected RCC. Intratumor gene therapy with polyethylenimine-loaded HIF-1α shRNA also resulted in tumor growth suppression. Thus, this study demonstrates that downregulation of HIF-1α could suppress tumorigenicity of RCC through induction of apoptosis, and HIF-1α shRNA may be a promising strategy for the treatment of RCC.

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Abbreviations

RNAi:

RNA interference

shRNA:

short-hairpin RNA

RCC:

renal cell carcinoma

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Authors and Affiliations

  1. Department of Urology, Huashan Hospital, Fudan University, Shanghai, China

    K Xu, Q Ding, Z Fang, J Zheng, P Gao, Y Lu & Y Zhang

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Correspondence to Q Ding.

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Xu, K., Ding, Q., Fang, Z. et al. Silencing of HIF-1α suppresses tumorigenicity of renal cell carcinoma through induction of apoptosis. Cancer Gene Ther 17, 212–222 (2010). https://doi.org/10.1038/cgt.2009.66

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