Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells
文献类型：期刊论文
| 作者 | Wang, Yue-qin1; Shen, Ai-jun2 ; Sun, Jing-ya2; Wang, Xin2; Liu, Hong-chun2; Zhang, Min-min2; Chen, Dan-qi3; Xiong, Bing3; Shen, Jing-kang3; Geng, Mei-yu2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2016-12 |
| 卷号 | 37期号:12页码:1587-1596 |
| ISSN号 | 1671-4083 |
| 关键词 | non-small cell lung cancer gefitinib resistance Hsp90 |
| DOI | 10.1038/aps.2016.85 |
| 文献子类 | Article |
| 英文摘要 | Aim: Inhibition of heat shock protein (Hsp90) has been proven to be effective in overriding primary and acquired resistance of kinase inhibitors. In this study, we investigated the role of FS-108, a newly developed Hsp90 inhibitor, to overcome gefitinib resistance in EGFR mutant non-small cell lung cancer cells. Methods: Cell proliferation was assessed using the SRB assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression was examined by Western blotting. The in vivo effectiveness of FS-108 was determined in an NCI-H1975 subcutaneous xenograft model. Results: FS-108 triggered obvious growth inhibition in gefitinib-resistant HCC827/GR6, NCI-H1650 and NCI-H1975 cells through inducing G(2)/M phase arrest and apoptosis. FS-108 treatment resulted in a remarkable degradation of key client proteins involved in gefitinib resistance and further abrogated their downstream signaling pathways. Interestingly, FS-108 alone exerted an identical or superior effect on circumventing gefitinib resistance compared to combined kinase inhibition. Finally, the ability of FS-108 to overcome gefitinib resistance in vivo was validated in an NCI-H1975 xenograft model. Conclusion: FS-108 is a powerful agent that impacts the survival of gefitinib-resistant cells in vitro and in vivo through targeting Hsp90. |
| WOS关键词 | TYROSINE KINASE INHIBITORS ; ACQUIRED-RESISTANCE ; MUTATIONS ; THERAPY |
| 资助项目 | Natural Science Foundation of China for Innovation Research Group[81321092] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development[00000000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020101] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020105] ; National Natural Science Foundation of China[91229205] ; National Natural Science Foundation of China[81402966] ; Shanghai Science and Technology Committee Foundation[124119b1900] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5867011 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| WOS记录号 | WOS:000389704500007 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275782]  |
| 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 药物化学研究室 |
| 通讯作者 | Geng, Mei-yu; Zheng, Min; Ding, Jian |
| 作者单位 | 1.China Pharmaceut Univ, Dept New Drug, Screening Ctr, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Synthet Organ & Med Chem Lab, Shanghai 201203, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Dept Thorac Surg, Shanghai 200336, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yue-qin,Shen, Ai-jun,Sun, Jing-ya,et al. Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells[J]. ACTA PHARMACOLOGICA SINICA,2016,37(12):1587-1596. |
| APA | Wang, Yue-qin.,Shen, Ai-jun.,Sun, Jing-ya.,Wang, Xin.,Liu, Hong-chun.,...&Ding, Jian.(2016).Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells.ACTA PHARMACOLOGICA SINICA,37(12),1587-1596. |
| MLA | Wang, Yue-qin,et al."Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells".ACTA PHARMACOLOGICA SINICA 37.12(2016):1587-1596. |
入库方式： OAI收割
来源：上海药物研究所
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