Open AccessNovel multiple tyrosine kinase inhibitor ponatinib inhibits bFGF-activated signaling in neuroblastoma cells and suppresses neuroblastoma growth in vivo
Author(s) -
Haoyu Li,
Yongfeng Wang,
Zhenghu Chen,
Jian Lu,
Jessie Pan,
Yu Ye,
Yanling Zhao,
Huiyuan Zhang,
Tian Hu,
Qing Liu,
Jianhua Yang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.11580
Subject(s) - ponatinib , cancer research , neuroblastoma , tyrosine kinase , in vivo , tyrosine kinase inhibitor , receptor tyrosine kinase , cell growth , biology , kinase , signal transduction , microbiology and biotechnology , pharmacology , medicine , chemistry , dasatinib , cell culture , cancer , biochemistry , genetics
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.