TFF3 Mediated Induction Of VEGF By Hypoxia In The Model Of Human Gastric Cancer BGC-823 Cells

Objective: Increasing evidence indicates that in gastric epithelial cells, induction of TFF3 by hypoxia is mediated by HIF-1. Since VEGF is one of the most important angiogenic factors on cancer progression, we have started to investigate the possible link among HIF-1α, VEGF and TFF3 in gastric cancer cells.Methods:⑴Using the CoCl2 to induce hypoxia condition and build hypoxic model of gastric cancer BGC-823 cell;⑵BGC-823 cells were transfected with pcPUR+U6 plasmid carrying RNAi targeted to human TFF3 and selected puromycin -resistant pools to establish the stable knockdown of TFF3 cells.⑶Using RT-PCR,Western blot and Elisa assay to detect the TFF3, VEGF and HIF-1a protein and mRNA expression in BGC-823 cell and TFF3-KD BGC-823 cell under normoxic and hypoxic condition;⑷using immunofluorescence staining to detect the distribution and expression of TFF3 and HIF-1αin BGC-823 cells under normoxia and hypoxia condition;Results:⑴Induction of HIF-1a via hypoxia and increased expressions of the TFF3 and VEGF in gastric cancer BGC-823 cell.⑵Stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia in BGC-823 cells.⑶Stable knockdown of TFF3 reduced the VEGF protein secretion induced by hypoxia in BGC-823 cells.Conclusion: Our data demonstrated the TFF3 mediated regulation of VEGF expression induced by hypoxia, and implicated that TFF3 might be applied as a potential anti-angiogenic target for treatment of gastric cancer.