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
Joint Authors
Shin, Tae Hwan
Han, Jeonghun
Lim, Wanyoung
You, Daeun
Jeong, Yisun
Kim, Sangmin
Lee, Jeong Eon
Park, Sungsu
Lee, Gwang
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-06-02
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Han, Jeonghun& Lim, Wanyoung& You, Daeun& Jeong, Yisun& Kim, Sangmin& Lee, Jeong Eon…[et al.]. 2019. 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. Journal of Oncology،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1183902
Modern Language Association (MLA)
Han, Jeonghun…[et al.]. 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. Journal of Oncology No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1183902
American Medical Association (AMA)
Han, Jeonghun& Lim, Wanyoung& You, Daeun& Jeong, Yisun& Kim, Sangmin& Lee, Jeong Eon…[et al.]. 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. Journal of Oncology. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1183902
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1183902