Suppressing the malignant phenotypes of glioma cells by lentiviral delivery of small hairpin RNA targeting hypoxia-inducible factor-1α

Hypoxic microenvironment of solid tumors is known to shape malignant phenotypes of cancer cells through the dimeric transcription factor hypoxia-inducible factor (HIF)-1. In the present study, the therapeutic effect of targeting a subunit of HIF-1 in glioma cells via lentiviral delivery of small hairpin RNA (shRNA) was evaluated. Data from quantitative real-time PCR and immunohistochemistry demonstrated that HIF-1 alpha was progressively upregulated during the development of gliomas. Lentiviral shRNA targeting HIF-1 alpha led to substantial loss of cell viability, G(0)/G(1)-phase cell cycle arrest, apoptosis, and impairment of cell motility and invasiveness in human glioma U87MG cells. Xenograft experiments in nude mice further showed that HIF-1 alpha-shRNA inhibited tumor growth and caused persistent repression of HIF-1 alpha and its target genes, including VEGF, GLUT1 and MMP2, up to 25 days post-inoculation. Taken together, lentiviral delivery of shRNA is a promising therapeutic approach for targeting HIF-1 alpha in glioma.