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 α 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-1α was progressively upregulated during the development of gliomas. Lentiviral shRNA targeting HIF-1α led to substantial loss of cell viability, G0/G1-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-1α-shRNA inhibited tumor growth and caused persistent repression of HIF-1α 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-1α in glioma.
Keywords: Hypoxia-inducible factor; glioma; lentivirus; short hairpin RNA.