title: DBD-F induces apoptosis in gastric cancer-derived cells through suppressing HIF2α expression.
abstract: OBJECTIVE
  Gastric cancer is the third leading cause of cancer-related death in China. Accumulating evidence indicates that HIF2α may affect the aggressiveness of gastric cancer. It has also been found that HIF2α C-terminal PAS domains can form complexes with inactive benzoxadiazole antagonists. Here, the anti-tumor effect of 4-(N,Ndimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) on human gastric cancer cells was examined using both in vitro and in vivo assays.
  
  
  RESULTS
  We found that DBD-F can induce apoptosis and inhibit the mobility of MKN28 and MKN45 gastric cancer-derived cells in vitro. We also found that DBD-F can suppress tumor growth in established gastric cancer-derived xenograft models in vivo. Finally, we found that DBD-F can inhibit HIF2α expression in gastric cancer-derived cells.
  
  
  CONCLUSIONS
  From our findings we conclude that DBD-F (i) is cytotoxic to gastric cancer-derived cells and (ii) can induce apoptosis in these cells via the MEK/ERK signaling pathway. In addition, our findings strongly indicate that DBD-F can inhibit HIF2α expression by affecting the phosphorylation status of MEK/ERK in gastric cancer-derived cells.
authors.affiliation: Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Tong
authors.affiliation: Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Tong
authors.affiliation: Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Qin
authors.affiliation: Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China. liuyong_sj@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D010080:Oxazoles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D010080:Oxazoles; D013449:Sulfonamides; D000099162:Endothelial PAS Domain-Containing Protein 1; C060548:4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole
keywords: Apoptosis; DBD-F; Gastric cancer; HIF2α; MEK/ERK