Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer
文献类型：期刊论文
| 作者 | Xie, Qin1,2; Chen, Hui2; Ai, Jing2 ; Gao, Ying-lei2; Geng, Mei-yu2; Ding, Jian2; Chen, Yi2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2017-11 |
| 卷号 | 38期号:11页码:1533-1542 |
| 关键词 | thyroid cancer AL3810 multi-tyrosine kinases inhibitor angiogenesis RET |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2017.107 |
| 文献子类 | Article |
| 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. |
| WOS关键词 | TARGETED THERAPIES ; RET ; CARCINOMA ; MODELS ; GROWTH ; TUMORS ; CELLS |
| 资助项目 | Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA01020304] ; National Natural Science Foundation of China[81521005] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:6092089 |
| WOS记录号 | WOS:000414248600011 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272424]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian; Chen, Yi |
| 作者单位 | 1.Nanchang Univ, Coll Pharm, Nanchang 330006, Jiangxi, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Qin,Chen, Hui,Ai, Jing,et al. Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer[J]. ACTA PHARMACOLOGICA SINICA,2017,38(11):1533-1542. |
| APA | Xie, Qin.,Chen, Hui.,Ai, Jing.,Gao, Ying-lei.,Geng, Mei-yu.,...&Chen, Yi.(2017).Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer.ACTA PHARMACOLOGICA SINICA,38(11),1533-1542. |
| MLA | Xie, Qin,et al."Evaluation of in vitro and in vivo activity of a multityrosine kinase inhibitor, AL3810, against human thyroid cancer".ACTA PHARMACOLOGICA SINICA 38.11(2017):1533-1542. |
入库方式： OAI收割
来源：上海药物研究所
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