Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer

摘要: // Hye-Young Kim 1, 2 , Yunhee Cho 3 HyeokGu Kang Ye-Seal Yim Seok-Jun Jaewhan Song Kyung-Hee Chun 1 Department of Biochemistry & Molecular Biology, Yonsei University College Medicine, Seodaemun-gu, Seoul 03722, Korea Biochemistry, Life Science and Biotechnology, Brain 21 PlusProject for Medical Science, University, Correspondence to: Chun, email: khchun@yuhs.ac Keywords: WEE1, AZD1775 (MK-1775), 5-FU, Paclitaxel, gastric cancer Received: September 07, 2015      Accepted: May 28, 2016      Published: June 23, 2016 ABSTRACT Wee1 is a member the Serine/Threonine protein kinase family key regulator cell cycle progression. It has been known that WEE1 highly expressed oncogenic functions in various cancers, but it not yet studied cancers. In this study, we investigated role therapeutic potency targeting cancer. At first, higher expression levels with lower survival probability were determined stage 4 patients or male accompanied lymph node metastasis. To determine function cells, ablation decreased proliferation, migration, invasion, while overexpression increased these effects cells. We also validated clinical application by small molecule, which specific inhibitor undergoing trials. significantly inhibited proliferation induced apoptosis arrest was more effective high-expressing Moreover, performed combination treatments anti-cancer agents, 5- fluorouracil Paclitaxel cells orthotopic-transplanted mice to maximize effect safety AZD1775. The dramatically tumor burdens stomach mice. Taken together, propose over-expressed could enhance Therefore, suggest potent target therapy.