The Effects Of Regulation Of Hypoxia-inducible Factor-1α On The Metastasis And Invasion Of Hypoxic Gastric Cancer Cells

Objective: To construct shRNA eukaryotic expression vector targeting HIF-1α, to investigate the relationship betweem hypoxia-inducible factor-1α(HIF-1α) and the invasion of hypoxic gastric cancer cells, to explore the possible mechanism of the effect of HIF-1αon the invasion ability of gastric cancer cells in hypoxia.Methods: To construct shRNA eukaryotic expression vector targeting HIF-1αand transfect it into SGC-7901 cells. Western blotting was used to detect the effect of RNAi targeting HIF-1α. To select the most effective plasmid to transfect into SGC-7901 cells and select the steadily transfected clones of HIF-lαRNAi. Western blotting, MTT and the Boyden chamber membrane invasion culture system were used to study the expression of HIF-lαand the adhesion, migration, invasion of human gastric cancer cells in hypoxia and HIF-1αRNAi. The expression of HIF-lα, MMP-9 and uPAR, which are invasion and metastasis related factors of gastric cancer, were detected by western blotting in hypoxia and HIF-1αRNAi.Results: The shRNA eukaryotic expression vector targeting HIF-1αwas successfully constructed. The expression of HIF-1αand the adhesion, migration and invasion abilities of human gastric cancer cells were significantly increased in hypoxia. The expression of HIF-1αand the adhesion, migration and invasion abilities of human gastric cancer cells were significantly decreased in RNAi. Meanwhile, the expression of HIF-1α, MMP-9 and uPAR were significantly increased in hypoxia. But the expression of HIF-1α, MMP-9 and uPAR were significantly decreased in RNAi.Conclusion: Hypoxia could positively regulate the expression of HIF-1αto promote the adhesion, migration and invasion abilities of human gastric cancer cells. The associated mechanism may be that HIF-1αcould positively regulate the expression of MMP-9 and uPAR. However, HIF-1αRNAi was contrary to this process.