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Neoplasma Vol.63, No.6, p.934-940,2016 |
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| Title: Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions | ||
| Author: J. CHEN, L. LAI, S. LIU, C. ZHOU, C. WU, M. HUANG, Q. LIN | ||
| Abstract: Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor to initiate the expressions of distinct pro-angiogenic growth genes, particularly the expression of vascular endothelial growth factor (VEGF). CoCl2 was used in rat liver tumor cell line McA RH-7777 to stimulate hypoxia to mimic the hypoxic conditions induced by transcatheter arterial chemoembolization (TACE). CCK8 assays were performed to examine the effect of hypoxia on cell viability. Real-time qRT-PCR, western blot and ELISA assays were used to measure the expression of HIF-1α and VEGF in McA RH-7777 cells under hypoxic conditions, respectively. Lentivirus-mediated HIF-1α and/or VEGF-specific shRNA was used to establish single or HIF-1α and VEGF double knocking-down McA RH-7777 cells. Transwell assays were performed to examine the effect of HIF-1α and VEGF knocking-down on McA RH-7777 cells migration and invasion. The mRNA and protein expression level of HIF-1α and VEGF were remarkably up-regulated in McA RH-7777 cells under hypoxic conditions, respectively. The knockdown of HIF-1α or VEGF significantly reduced the expression of the secreted VEGF. More importantly, knockdown of both HIF-1α and VEGF resulted in the best effective inhibitory effect in VEGF expression, and in turn remarkably reduced the cell migration and invasion activity. Our findings showed that HIF-1α play an important role in the stimulation of the secreted VEGF expression under hypoxic conditions, suggesting that targeting both HIF-1α and VEGF could represent a potential therapeutic strategy in combination with TACE in the treatment of liver tumors. |
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| Keywords: liver tumor, hepatocellular carcinoma, transcatheter arterial chemoembolization, hypoxia-inducible factor-1α, vascular endothelial growth factor | ||
| Published online: 16-Nov-2016 | ||
| Year: 2016, Volume: 63, Issue: 6 | Page From: 934, Page To: 940 | |
| doi:10.4149/neo_2016_612 |
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