Cancer - Bladder, Pelvis, Ureter & Others(구연) Oral Session 4 / Cancer - Bladder, Pelvis, Ureter & Others (Ⅰ) (O-039) Geumkang Hall (Avenue 2F) 11월28일(수) 13:00-14:00 Multikinase inhibitor motesanib enhances the antitumor effect of cisplatin in cisplatin-resistant human bladder cancer cells via apoptosis and the PI3K/Akt pathway Department of Urology, Seoul National University Bundang Hospital¹ Wide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, South Korea² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080 South Korea³ HOYOUNG RYU¹, JIN-NYOUNG HO¹, SEOK-SOO BYUN¹, SANG EUN LEE¹, JE-IN YOUN²³, SANGCHUL LEE¹ Motesanib (AMG706) is a small organic molecule that acts as a multi-targeted tyrosine kinase inhibitor of VEGF receptor, PDGF receptor and stem cell factor receptor. It exhibits a potent antitumor effect in vitro and in vivo. To investigate the anticancer effect and possible mechanisms of motesanib in cisplatin-resistant human bladder cancer cells (T24R2), T24R2 cells were treated with motesanib (50 μM) with or without cisplatin (2.5 μg/mL). Cell growth was measured by the Cell Counting Kit-8 assay and clonogenic assay. Cell cycle progression and apoptotic cell death were examined using flow cytometry. Expression levels of apoptosis- and survival-related proteins were determined by western blot analysis. In combination with cisplatin, motesanib exhibited synergistic inhibition on T24R2 cell growth. Treatment using motesanib in combination with cisplatin remarkably induced apoptosis and promoted cell cycle arrest in the S phase. It also increased the expression of apoptosis-related genes including caspases, poly (ADP-ribose) polymerase, and cytochrome c, whereas it decreased the expression of survival-related genes including p-PI3K and p-Akt. In conclusion, combination treatment with motesanib and cisplatin showed a synergistically enhanced anticancer effect on cisplatin resistant human bladder cancer cells, accompanied with induced apoptosis and cell cycle arrest. Thus, the multikinase inhibitor motesanib could be developed as possible therapeutic agent for bladder cancer. keywords : bladder cancer cells, motesanib, multikinase inhibitor, apoptosis