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
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 |
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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 |
Description not available. |