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

Abstract

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. 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. 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.

DOI: 10.1007/s13402-015-0253-5

Extracted Key Phrases

6 Figures and Tables

Cite this paper

@article{Tong2015DBDFIA, title={DBD-F induces apoptosis in gastric cancer-derived cells through suppressing HIF2α expression}, author={Guang-Hui Tong and Wei-Wei Tong and Xiao-song Qin and Li-ping Lu and Yong Liu}, journal={Cellular Oncology}, year={2015}, volume={38}, pages={479-484} }