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17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells

文献类型：期刊论文

作者Zuo, Yu1; Xu, Heng2,3,4; Chen, Zhifeng2,3; Xiong, Fengmin1; Zhang, Bei2,3; Chen, Kaixian2,3,4; Jiang, Hualiang2,3,4; Luo, Cheng2,3,4; Zhang, Hao2,3,4
刊名ONCOLOGY REPORTS
出版日期2020-03-26
卷号43期号:6页码:1928-1944
关键词triple-negative breast cancer heat shock protein 90 inhibitor histone deacetylase 6 inhibitor synergistic
ISSN号1021-335X
DOI10.3892/or.2020.7563
文献子类Article
英文摘要Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug-resistance and metastasis. Drug combination can help to reduce the adverse side effects of chemotherapies using single drugs, and also help to overcome common drug-resistance during clinical treatment of breast cancer. The present study reported the synergistic effect of the heat shock protein 90 inhibitor 17-AAG and the histone deacetylase 6 inhibitor Belinostat in triple-negative breast cancer (TNBC) MDA-MB-231 cells, by detection of proliferation, apoptosis and cell cycle arrest following treatment with this combination. Subsequently, RNA sequencing (RNA-seq) data was collected and analyzed to investigate the synergistic mechanism of this combination. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways revealed by RNA-seq data analysis, a wound-healing assay was used to investigate the effect of this combination on the migration of MDA-MB-231 cells. Compared with treatment with 17-AAG or Belinostat alone, both the viability inhibition and apoptosis rate of MDA-MB-231 cells were significantly enhanced in the combination group. The combination index values were <1 in three concentration groups. Revealed by the RNA-seq data analysis, the most significantly enriched KEGG pathways in the combination group were closely associated with cell migration. Based on these findings, the anti-migration effect of this combination was investigated. It was revealed that the migration of MDA-MB-231 cells was significantly suppressed in the combination group compared with in the groups treated with 17-AAG or Belinostat alone. In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group. These alterations may help to explain the anti-migration effect of this combination. Belinostat has already been approved as a treatment for T-cell lymphoma and 17-AAG is undergoing clinical trials. These findings could provide a beneficial reference for the clinical treatment of patients with TNBC.
WOS关键词HISTONE-DEACETYLASE INHIBITOR ; SHOCK-PROTEIN 90 ; THERAPEUTIC TARGETS ; CARCINOMA-CELLS ; HSP90 ; COMBINATION ; EXPRESSION ; APOPTOSIS ; PATHWAY ; HDAC6
WOS研究方向Oncology
语种英语
WOS记录号WOS:000530363200019
出版者SPANDIDOS PUBL LTD
源URL[http://119.78.100.183/handle/2S10ELR8/309415]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Zhang, Hao
作者单位1.Nanchang Univ, Sch Pharm, Dept Pharm, Nanchang 330006, Jiangxi, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Drug Discovery, 555 Zu Chongzhi Rd, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Design Ctr, 555 Zu Chongzhi Rd, Shanghai 201203, Peoples R China;
4.Univ Chinese Acad Sci, Dept Pharm, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Zuo, Yu,Xu, Heng,Chen, Zhifeng,et al. 17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells[J]. ONCOLOGY REPORTS,2020,43(6):1928-1944.
APA Zuo, Yu.,Xu, Heng.,Chen, Zhifeng.,Xiong, Fengmin.,Zhang, Bei.,...&Zhang, Hao.(2020).17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells.ONCOLOGY REPORTS,43(6),1928-1944.
MLA Zuo, Yu,et al."17-AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA-MB-231 breast cancer cells".ONCOLOGY REPORTS 43.6(2020):1928-1944.

入库方式： OAI收割

来源：上海药物研究所

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