Academic Journal

Chemoresistance in the Human Triple-Negative Breast Cancer Cell Line MDA-MB-231 Induced by Doxorubicin Gradient Is Associated with Epigenetic Alterations in Histone Deacetylase

Bibliographic Details
Title: Chemoresistance in the Human Triple-Negative Breast Cancer Cell Line MDA-MB-231 Induced by Doxorubicin Gradient Is Associated with Epigenetic Alterations in Histone Deacetylase
Authors: Han, Jeonghun, Lim, Wanyoung, You, Daeun, Jeong, Yisun, Kim, Sangmin, Lee, Jeong Eon, Shin, Tae Hwan, Lee, Gwang, Park, Sungsu
Publisher Information: Hindawi
Publication Year: 2019
Collection: PubMed Central (PMC)
Subject Terms: Research Article
Description: Chemoresistance is one of the major causes of therapeutic failure in breast cancer patients. In this study, the mechanism of chemoresistance in human triple-negative breast cancer (TNBC) cells (MDA-MB-231) induced by doxorubicin (DOX) gradient was investigated. These DOX-resistant cells showed higher drug efflux rate, increased anchorage-independent growth when cultured in suspension, and increased tumor-forming ability in nude mice, compared to the wild-type MDA-MB-231 cells. RNA sequencing analysis showed an increase in the expression of genes involved in membrane transport, antiapoptosis, and histone regulation. Kaplan-Meier plot analysis of TNBC patients who underwent preoperative chemotherapy showed that the relapse free survival (RFS) of patients with high HIST1H2BK (histone cluster 1 H2B family member k) expression was significantly lower than that of patients with low HIST1H2BK expression. Quantitative real-time PCR confirmed that the level of HIST1H2BK expression was increased in resistant cells. The cytotoxicity analysis showed that the DOX resistance of resistant cells was reduced by treatment with a histone deacetylase (HDAC) inhibitor. Our results suggest that, in DOX-resistant cells, HIST1H2BK expression can be rapidly induced by the high expression of genes involved in membrane transport, antiapoptosis, and histone regulation. In conclusion, chemoresistance in MDA-MB-231 cells can occur in a relatively short period by DOX gradient via this previously known mechanism of resistance, and DOX resistance is dependent on the specificity of resistant cells to HDAC.
Document Type: text
Language: English
Relation: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582875/; http://dx.doi.org/10.1155/2019/1345026
DOI: 10.1155/2019/1345026
Availability: https://doi.org/10.1155/2019/1345026
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582875/
Rights: Copyright © 2019 Jeonghun Han et al. ; https://creativecommons.org/licenses/by/4.0/ ; This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Accession Number: edsbas.FF53FA41
Database: BASE
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