The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells by down-regulating HSPB8
文献类型：期刊论文
| 作者 | Shi, Jia-jie1,2; Chen, Si-meng2; Guo, Chen-Liang2; Li, Yi-xue3; Ding, Jian1,2 ; Meng, Ling-hua1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2018-08 |
| 卷号 | 39期号:8页码:1338-1346 |
| 关键词 | tamoxifen resistance HSPB8 AZD8055 estrogen receptor mTOR inhibitor |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2017.181 |
| 文献子类 | Article |
| 英文摘要 | Tamoxifen, an important endocrine therapeutic agent, is widely used for the treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alternative treatments. In this study, we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen (MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates with poor prognosis in ER+ breast cancer patients but not in patients without classification. Stimulating ER signaling by heterogeneous expression of ERa or 17 beta-estradiol promotes HSPB8 expression and reduces the cell population in G(1) phase. In contrast, blockage of ER signaling by tamoxifen down-regulates the expression of HSPB8. In addition, knocking down HSPB8 by specific siRNAs induces significant cell cycle arrest at G(1) phase. AZD8055 was found to be more potent against the proliferation of MCF-7/R cells than that of parent cells, which was associated with down-regulation of HSPB8. We found that the anti-proliferative activity of AZD8055 was positively correlated with the HSPB8 expression level in ER+ breast cancer cells. Thus, AZD8055 was able to overcome tamoxifen resistance in breast cancer cells, and the expression of HSPB8 may predict the efficacy of AZD8055 in ER+ breast cancer. This hypothesis deserves further investigation. |
| WOS关键词 | HEAT-SHOCK-PROTEIN ; ENDOCRINE RESISTANCE ; MECHANISMS ; GROWTH ; PROLIFERATION ; EVEROLIMUS ; PROGNOSIS ; KINASE ; TARGET |
| 资助项目 | National Natural Science Foundation of China[81373445] ; Chinese Academy of Sciences[XDA12020202] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:6309898 |
| WOS记录号 | WOS:000441241700009 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279634]  |
| 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; Meng, Ling-hua |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Shanghai Ctr Bioinformat Technol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shi, Jia-jie,Chen, Si-meng,Guo, Chen-Liang,et al. The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells by down-regulating HSPB8[J]. ACTA PHARMACOLOGICA SINICA,2018,39(8):1338-1346. |
| APA | Shi, Jia-jie,Chen, Si-meng,Guo, Chen-Liang,Li, Yi-xue,Ding, Jian,&Meng, Ling-hua.(2018).The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells by down-regulating HSPB8.ACTA PHARMACOLOGICA SINICA,39(8),1338-1346. |
| MLA | Shi, Jia-jie,et al."The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells by down-regulating HSPB8".ACTA PHARMACOLOGICA SINICA 39.8(2018):1338-1346. |
入库方式： OAI收割
来源：上海药物研究所
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