title: Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions.
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.
authors: J
authors: J
authors: Chen
authors: L
authors: L
authors: Lai
authors: S
authors: S
authors: Liu
authors: C
authors: C
authors: Zhou
authors: C
authors: C
authors: Wu
authors: M
authors: M
authors: Huang
authors: Q
authors: Q
authors: Lin
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D016086:Lentivirus; D008113:Liver Neoplasms / Q000188:drug therapy*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: hepatocellular carcinoma; hypoxia-inducible factor-1α vascular endothelial growth factor.; liver tumor; transcatheter arterial chemoembolization