title: TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells.
abstract: 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. We induced the hypoxic condition in SGC-7901cells using hypoxia-mimetic agent of CoCI2. SGC7901 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. Our results showed the induction of HIF-1a via hypoxia and consequences of increased expressions of the TFF3 and VEGF in gastric cancer SGC-7901 cells. Overexpression of TFF3 upregulated the mRNA expressions of VEGF and HIF-1a induced by hypoxia, and stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia. Furthermore, knockdown of TFF3 reduced the VEGF protein secretion: as VEGF secretion was increased time dependent manner in response to the hypoxia induction in TFF3-WT cells; however, VEGF production was significantly decreased in TFF3-KD cells (621 ± 89 vs. 264 ± 73 at 6 h and 969 ± 97 vs. 508 ± 69 at 12 h, P < 0.05). 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.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, 201 Hubin South Road, Xiamen, 361004, Fujian, China. bayasi8@gmail.com
authors.forename: Bayasi
authors.initials: B
authors.lastname: Guleng
authors.forename: Jia
authors.initials: J
authors.lastname: Han
authors.forename: Jin-Qiu
authors.initials: JQ
authors.lastname: Yang
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Huang
authors.forename: Jian-Kun
authors.initials: JK
authors.lastname: Huang
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Yang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Liu
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Ren
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics*; D000071165:Trefoil Factor-3; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010455:Peptides; D012333:RNA, Messenger; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A