MP88-04 ANTI-TUMOR EFFECT OF NEW TYROSIN KINASE INHIBITORS (BOSUTINIB, NINTEDANIB, VATALANIB) IN HUMAN BLADDER CANCER CELLS

Abstract

INTRODUCTION AND OBJECTIVES: Angiogenesis is known to play a major role in the pathogenesis of bladder cancer. Bosutinib is an orally bioavailable dual Src/Abl tyrosin kinase inhibitor (TKI). Nintedanib and vatalanib are TKI that inhibits the vascular endothelial growth factor receptor (VEGFR) and the platelet-derived growth factor receptor (PDGFR), has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. We examined anti-tumor effects of bosutinib, nintedanib, and vatalanib in human bladder cancer cells (T24, cisplatinresistant-T24R2). METHODS: Bladder cancer cells were treated with bosutinib, nintedanib, and vatalanib and cancer cell proliferation was determined using the cell counting kit-8 (CCK-8) assay and clonogenic assay. Cell cycle and apoptosis rate were measured by flow cytometry. Apoptosisand cell cycle-related protein expression was analyzed by Western blot assays. RESULTS: Bladder cancer cell proliferation and colony formation was significantly reduced by bosutinib and vatalanib treatment in a dose-dependent manner. Bosutinib, nintedanib, and vatalanib induced apoptosis and cell cycle arrest at G1 phase. Expression of apoptosis related proteins (caspase-3, -8, -9, PARP, cytochrome c, bad, and bax) was elevated by bosutinib, nintedanib, and vatalanib treatment. CONCLUSIONS: In conclusion, new TKI (bosutinib, nintedanib, and vatalanib) showed anticancer effect in bladder cancer cells through induce apoptosis and cell cycle arrest. These data suggest that bosutinib, nintedanib, and vatalanib may be a novel therapeutic approach in the bladder cancer.