Biological characteristics of prostate cancer cells are regulated by hypoxia-inducible factor 1α

摘要

Hypoxia-inducible factor (HIF)-1α has been reported to be associated with malignancy in a number of types of cancer. However, the role of HIF-1 α in the regulation of prostate cancer (PCa) growth has yet to be elucidated. The present study aimed to investigate the effect of HIF-1α on the biological characteristics of the PCa PC3 cell line. Full-length (fL) HIF-1α and dominant-negative (dn) HIF-1α were transfected into PC3 cells. The expression of HIF-1α and its downstream genes, including vascular endothelial growth factor (VEGF), erythropoietin (EPO) and CXC chemokine receptor 4 (CXCR4), were detected using western blot analysis. Cell proliferation, apoptosis and migration were assessed using MTT, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Boyden chamber assays. The expression of VEGF, EPO and CXCR4 was found to be upregulated in the fL HIF-1α-transfected PC3 cells and downregulated in the dn HIF-1α-transfected PC3 cells. The overexpression of HIF-1α was observed to enhance cell proliferation and migration and decrease docetaxol-induced cell apoptosis. However, dn HIF-1α was found to attenuate cell proliferation and migration, and promote docetaxol-induced cell apoptosis. These findings indicate that HIF-1α regulates the proliferation, apoptosis and migration of PC3 cells, at least in part, by regulating the expression of its target genes, including VEGF, EPO and CXCR4. Thus, the use of HIF-1α inhibitors may be a promising therapy for the treatment of PCa.