期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 13, 期 4, 页码 505-517出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.18834
关键词
Breast cancer; TNBC; HSP90; HDAC6; tamoxifen resistance
资金
- National Basic Research Program of China (973 Program) [2015CB965000, 2013CB911300]
- National Natural Science Foundation of China [81572712, 81272260, 81572928, 81272469]
- Fundamental Research Funds for the Central Universities [3231005410]
- clinical special project for Natural Science Foundation of Jiangsu Province [BL2012016]
- Jiangsu Natural Science Foundation Outstanding Youth Foundation [SBK2016030027]
- Six talent peaks project in Jiangsu Province [2015-JY-002]
Breast cancer is the leading cause of women death. Heat shock protein 90 (HSP90) and Histone deacetylase 6 (HDAC6) are promising anti-cancer drug targets. However, it's still unclear the applicability of anti-HSP90 and anti-HDAC6 strategies in precision treatment of breast cancer. In current study, we found that triple negative breast cancer (TNBC) cells, compared to T47D, an ER alpha+ breast cancer cell line, exhibited 7 similar to 40 times lower IC50 values, stronger cell cycle perturbation, increased cell apoptosis and stronger inhibition of cell migration upon 17-DMAG treatment, while T47D, compared to TNBC cells, expressed higher HDAC6 and showed stronger anti-cancer response upon treatment of Tubacin. Mechanically, 17-DMAG treatment inhibited a complex network consists at least ERK, AKT, and Hippo pathway in TNBC cells, and higher expression of HDAC6 inhibited HSP90 activity via deacetylating HSP90. Furthermore, we found higher HDAC6 expression level in tamoxifen-resistance T47D than that in T47D, and Tubacin treatment suppressed the growth of tamoxifen-resistant cells in vivo. Our data suggested that anti-HSP90 and anti-HDAC6 are promising strategies to treat TNBC and ERa+ breast cancers respectively, and anti-HDAC6 can be considered during treatment of tamoxifen-resistance breast cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据