AZD-4547 exerts potent cytostatic and cytotoxic activities against fibroblast growth factor receptor (FGFR)-expressing colorectal cancer cells

• DOI: 10.1007/s13277-015-3237-1
• Publication Date: 2015-02-18T06:47:20Z
• Authors: Ting-Jing Yao; Jin-Hai Zhu; De-Feng Peng; Zhen Cui; Chao Zhang; Pei-hua Lu
• Keywords: 0301 basic medicine; Carcinogenesis; MAP Kinase Signaling System; TOR Serine-Threonine Kinases; HCT116 Cells; Xenograft Model Antitumor Assays; Piperazines; 3. Good health; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Benzamides; Animals; Humans; Pyrazoles; Receptor, Fibroblast Growth Factor, Type 1; Colorectal Neoplasms; HT29 Cells; Signal Transduction

Colorectal cancer (CRC) causes significant mortalities worldwide. Fibroblast growth factor (FGF) receptor (FGFR) signaling is frequently dysregulated and/or constitutively activated in CRCs, contributing to carcinogenesis and progression. Here, we studied the activity of AZD-4547, a novel potent FGFR kinase inhibitor, on CRC cells. AZD-4547 inhibited cell vitro, its correlated with FGFR-1/2 expression level. was cytotoxic pro-apoptotic FGFR-1/2-expressed lines (NCI-H716 HCT-116), but not null HT-29 Further, cycle progression attenuated activation FGFR1-FGFR substrate 2 (FRS-2), ERK/mitogen-activated protein (MAPK), AKT/mammalian target rapamycin (AKT/mTOR) signalings NCI-H716 HCT-116 In vivo, oral administration at effective doses (high expression) xenograft nude mice. Phosphorylation FGFR-1, AKT, ERK1/2 specimens also by administration. Thus, our preclinical studies strongly support possible clinical investigations for treatment CRCs harboring deregulated signalings.