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 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.
['Dong|Chang Gui|CG|', 'Wu|William K K|WK|', 'Feng|Su Yin|SY|', 'Yu|Jun|J|', 'Shao|Jun Fei|JF|', 'He|Gui Mei|GM|']
D000818:Animals D017209:Apoptosis D001932:Brain Neoplasms D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D002465:Cell Movement D002470:Cell Survival D005260:Female D015972:Gene Expression Regulation, Neoplastic D018014:Gene Transfer Techniques D015316:Genetic Therapy D005822:Genetic Vectors D005910:Glioma D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D016086:Lentivirus D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D009361:Neoplasm Invasiveness D010641:Phenotype D034622:RNA Interference D034741:RNA, Small Interfering D013997:Time Factors D014162:Transfection D047368:Tumor Burden D023041:Xenograft Model Antitumor Assays
glioma Hypoxia-inducible factor lentivirus short hairpin RNA