Home HOME Neoplasma 2016 Neoplasma Vol.63, No.6, p.934-940,2016

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.63, No.6, p.934-940,2016

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.

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

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