AT-101 inhibits hedgehog pathway activity and cancer growth
文献类型：期刊论文
| 作者 | Wang, Juan1; Peng, Yuanqiu1; Liu, Yuan1; Yang, Jun1; Huang, Ming2; Tan, Wenfu1,2 |
| 刊名 | CANCER CHEMOTHERAPY AND PHARMACOLOGY
 |
| 出版日期 | 2015-09 |
| 卷号 | 76期号:3页码:461-469 |
| 关键词 | Hedgehog AT-101 Gossypol Medulloblastoma Smoothened |
| ISSN号 | 0344-5704 |
| DOI | 10.1007/s00280-015-2812-x |
| 文献子类 | Article |
| 英文摘要 | AT-101 is considered as a putative pan-inhibitor of anti-apoptotic Bcl-2 family protein members acting as a BH3 mimetic. It is currently being investigated in phase I/II clinical trial in various types of cancers. In this study, using a series of in vitro and in vivo assays, we evaluated the effect of AT-101 on the hedgehog (Hh) signaling pathway activity and its anticancer ability. We found that AT-101 obviously blocked the Hh signaling pathway activity in response to ShhN-conditioned medium (ShhN CM). This inhibitory effect, to some extent, displayed selectivity against Hh signaling pathway. Furthermore, we identified that AT-101 potentially acted on smoothened (Smo) by sharing the same binding site with cyclopamine, a classical Hh signaling pathway inhibitor. Taking advantage of the patch+/-; p53-/- mouse medulloblastoma model, we observed that AT-101 significantly suppressed the Hh-driven medulloblastoma growth in vitro and in vivo. This study demonstrates that AT-101 significantly and selectively inhibits Hh pathway activity by potentially targeting Smo and consequently suppresses the growth of Hh-driven cancer. Therefore, this study reveals a novel molecular mechanism responsible for the anticancer action of AT-101 and contributes to the further development of AT-101 as an anticancer drug. |
| WOS关键词 | CELL LUNG-CANCER ; SMALL-MOLECULE INHIBITOR ; PROSTATE-CANCER ; IN-VIVO ; ENDOPLASMIC-RETICULUM ; PHASE I/II ; GOSSYPOL ; ANTAGONISTS ; PROTEINS ; BCL-2 |
| 资助项目 | Shanghai Municipal Science & Technology Pillar Program for Bio-pharmaceuticals[14431900400] ; State Key Laboratory of Drug Research[SIMM1501KF-09] |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000359817800003 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276425]  |
| 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 | Tan, Wenfu |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Juan,Peng, Yuanqiu,Liu, Yuan,et al. AT-101 inhibits hedgehog pathway activity and cancer growth[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2015,76(3):461-469. |
| APA | Wang, Juan,Peng, Yuanqiu,Liu, Yuan,Yang, Jun,Huang, Ming,&Tan, Wenfu.(2015).AT-101 inhibits hedgehog pathway activity and cancer growth.CANCER CHEMOTHERAPY AND PHARMACOLOGY,76(3),461-469. |
| MLA | Wang, Juan,et al."AT-101 inhibits hedgehog pathway activity and cancer growth".CANCER CHEMOTHERAPY AND PHARMACOLOGY 76.3(2015):461-469. |
入库方式： OAI收割
来源：上海药物研究所
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