Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions

Rok, strany: 2016, 934 - 940

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

ISO 690:

Chen, J., Lai, L., Liu, S., Zhou, C., Wu, C., Huang, M., Lin, Q. 2016. Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions. In NEOPLASMA, vol. 63, no.6, pp. 934-940. 0028-2685.

APA:

Chen, J., Lai, L., Liu, S., Zhou, C., Wu, C., Huang, M., Lin, Q. (2016). Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions. NEOPLASMA, 63(6), 934-940. 0028-2685.