DBD-F induces apoptosis in gastric cancer-derived cells through suppressing HIF2α expression

Purpose Gastric cancer is the third leading cause of cancer-related death in China. Accumulating evidence indicates that HIF2 alpha may affect the aggressiveness of gastric cancer. It has also been found that HIF2 alpha 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. Methods and 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 HIF2 alpha 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 HIF2 alpha expression by affecting the phosphorylation status of MEK/ERK in gastric cancer-derived cells.