evaluationofinvitroandinvivoactivityofamultityrosinekinaseinhibitoral3810againsthumanthyroidcancer

doi:10.1038/aps.2017.107

	evaluationofinvitroandinvivoactivityofamultityrosinekinaseinhibitoral3810againsthumanthyroidcancer
	Xie Qin 2; Chen Hui 1; Al Jing 1; Gao Yinglei 1; Geng Meiyu 1; Ding Jian 1; Chen Yi 1
刊名	actapharmacologicasinica
	2017
卷号	38 期号:11 页码:1533
关键词	TARGETED THERAPIES RET CARCINOMA MODELS GROWTH TUMORS CELLS thyroid cancer AL3810 multi-tyrosine kinases inhibitor angiogenesis RET
ISSN号	1671-4083
DOI	10.1038/aps.2017.107
英文摘要	Thyroid cancer is the most common type of endocrine neoplasia. Despite recent breakthroughs in treatment of the disease, the treatment of advanced, progressive thyroid cancers remains challenging with limited therapeutic options available. In this study, we evaluated a novel and orally bioavailable small-molecule multiple tyrosine kinases inhibitor, AL3810, in preclinical models of thyroid cancer in vitro and in vivo. AL3810 (2-5 mu mol/L) dose-dependently inhibited the proliferation of human thyroid cancer cell lines TT, SW579 and TPC-1 in vitro with IC50 values ranging from 0.59 to 7.03 mu mol/L. Specifically, this agent dose-dependently arrested the thyroid cancer cells in the G(1) phase and induced apoptosis. Furthermore, AL3810 dose-dependently inhibited the migration and invasion of SW579 and TPC-1 cells in vitro. In SW579 and TT xenograft models, oral administration of AL3810 (5-20 mg.kg(-1).d(-1))for 21 d potently inhibited the tumor growth; immunohistochemical staining revealed that the antitumor activity of AL3810 was closely correlated with its anti-angiogenesis effect, as evidenced by a dose-dependent reduction of microvessels in tumor tissues. To assess the therapeutic potential of AL3810 in treating thyroid cancer involving RET gene fusion, we showed that AL3810 (1-10 mu mol/L) dose-dependently inhibited the proliferation of RET-driven Baf3 cell line Baf3-CCDC6-RET, and the auto-phosphorylation of RET in these cells. Our data suggest that AL3810 is a promising agent for the treatment of thyroid cancer.
资助项目	[Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences] ; [National Natural Science Foundation of China]
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/287222]
专题	中国科学院上海药物研究所
作者单位	1.中国科学院上海药物研究所 2.南昌大学
推荐引用方式 GB/T 7714	Xie Qin,Chen Hui,Al Jing,et al. evaluationofinvitroandinvivoactivityofamultityrosinekinaseinhibitoral3810againsthumanthyroidcancer[J]. actapharmacologicasinica,2017,38(11):1533.
APA	Xie Qin.,Chen Hui.,Al Jing.,Gao Yinglei.,Geng Meiyu.,...&Chen Yi.(2017).evaluationofinvitroandinvivoactivityofamultityrosinekinaseinhibitoral3810againsthumanthyroidcancer.actapharmacologicasinica,38(11),1533.
MLA	Xie Qin,et al."evaluationofinvitroandinvivoactivityofamultityrosinekinaseinhibitoral3810againsthumanthyroidcancer".actapharmacologicasinica 38.11(2017):1533.