title: Novel multiple tyrosine kinase inhibitor ponatinib inhibits bFGF-activated signaling in neuroblastoma cells and suppresses neuroblastoma growth in vivo.
abstract: Neuroblastoma (NB) is one of the most common pediatric malignancies in children. Abnormal activation of receptor tyrosine kinases contributes to the pathological development of NB. Therefore, targeting tyrosine kinase receptors to cure NB is a promising strategy. Here, we report that a multi-targeted tyrosine kinase inhibitor ponatinib inhibited NB cell proliferation and induced NB cell apoptosis in a dose-dependent manner. In addition, ponatinib suppressed the colony formation ability of NB cells. Mechanistically, ponatinib effectively inhibited the FGFR1-activated signaling pathway. Ponatinib also enhanced the cytotoxic effects of doxorubicin on NB cells. Furthermore, ponatinib demonstrated anti-tumor efficacy in vivo by inhibiting tumor growth in an orthotopic xenograft NB mouse model. In summary, our results showed that ponatinib inhibited NB growth both in vitro and in vivo.
authors: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.|The Institute of Skull Base Surgery and Neurooncology at Hunan Province, 410008, China.|Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Haoyu
authors: H
authors: Li
authors: Department of Microbiology, Peking University Health Science Center, Beijing 100191, China.|Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Yongfeng
authors: Y
authors: Wang
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P. R. China.
authors: Zhenghu
authors: Z
authors: Chen
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Jiaxiong
authors: J
authors: Lu
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Jessie
authors: J
authors: Pan
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Yang
authors: Y
authors: Yu
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Yanling
authors: Y
authors: Zhao
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Huiyuan
authors: H
authors: Zhang
authors: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.|The Institute of Skull Base Surgery and Neurooncology at Hunan Province, 410008, China.|Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Ting
authors: T
authors: Hu
authors: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.|The Institute of Skull Base Surgery and Neurooncology at Hunan Province, 410008, China.
authors: Qing
authors: Q
authors: Liu
authors: Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Jianhua
authors: J
authors: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D011724:Pyridazines / Q000008:administration & dosage* / Q000494:pharmacology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D016222:Fibroblast Growth Factor 2; C545373:ponatinib; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D004318:Doxycycline
keywords: FGFR1; apoptosis; chemoresistance; neuroblastoma; ponatinib