期刊
ONCOTARGET
卷 8, 期 4, 页码 5874-5884出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11580
关键词
neuroblastoma; ponatinib; FGFR1; apoptosis; chemoresistance
资金
- NIH/NINDS grants [1R01NS072420, 1R21NS085467, 1R21NS094654]
- National Key Technology Research and Development Program of the Ministry of Science and Technology of China [2014BAI04B02]
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.
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