Guang-Hui Tong1, Wei-Wei Tong1, Xiao-Song Qin1, Li-Ping Lu1, Yong Liu2. 1. Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China. 2. Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang, 110004, China. liuyong_sj@163.com.
Abstract
PURPOSE: 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. 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 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.
PURPOSE: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 humangastric 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 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: Barbara Chiavarina; Ubaldo E Martinez-Outschoorn; Diana Whitaker-Menezes; Anthony Howell; Herbert B Tanowitz; Richard G Pestell; Federica Sotgia; Michael P Lisanti Journal: Cell Cycle Date: 2012-08-16 Impact factor: 4.534
Authors: S Chung; J Yao; K Suyama; S Bajaj; X Qian; O D Loudig; E A Eugenin; G R Phillips; R B Hazan Journal: Oncogene Date: 2012-03-12 Impact factor: 9.867