| Autor: |
Hung Huynh, Khee Chee Soo, Jonathan Lee, Pierce Chow, Alexander Chung, Hock Soo Ong, Heng Nung Koong, Choon Hua Thng, Wei Ling Irene Lam, Wei Jie Richard Ong, Swee Shean Lee, Lih Wen Valerie Chong, Guo Bin Lew, Van Chanh Ngo, Shu Yang |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1535-7163.c.6531696.v1 |
| Popis: |
Gastric cancer is a deadly disease for which current therapeutic options are extremely limited. Vascular endothelial growth factor receptors and platelet-derived growth factor receptors regulate gastric cancer cell proliferation, invasion, and tumor angiogenesis. In the present study, we report that sorafenib therapy effectively inhibited tumor growth and angiogenesis in tumor xenografts. These were associated with reduction in the phosphorylation of vascular endothelial growth factor receptor-2 Tyr951, c-Kit Tyr568/570, platelet-derived growth factor receptor-β Tyr1021, and Akt Ser473 and Thr308, down-regulation of positive cell cycle regulators, increased apoptosis, and up-regulation of p27. Sorafenib treatment also caused up-regulation of p-c-Raf Ser338 and p-extracellular signal-regulated kinase (ERK) Thr202/Tyr204 in gastric cancer xenografts. The combination of sorafenib and MAP/ERK kinase inhibitor AZD6244 enhances the effectiveness of each compound alone. Potential effect of sorafenib/AZD6244 included increase in proapoptotic Bim. Our data show that MAP/ERK kinase inhibition enhances the antitumor activity of sorafenib in vivo, supporting a rationale for multitargeted suppression of the angiogenesis and ERK signaling network in gastric cancer therapy. [Mol Cancer Ther 2009;8(9):2537–45] |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
