Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells

Apoptosis : an International Journal on Programmed Cell Death
Li-han ZhangMin Li

Abstract

Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.

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Citations

Sep 25, 2017·Apoptosis : an International Journal on Programmed Cell Death·Zhengzhi ZouSongmao Wang
Jul 17, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hui-Yu LinYuan-Feng Lin
Jun 26, 2017·Chinese Journal of Cancer·Ying-Jie LiZhe-Sheng Chen
Dec 5, 2018·Proceedings of the National Academy of Sciences of the United States of America·Caigang LiuQiyong Guo
Nov 27, 2020·Journal of Hematology & Oncology·Haocai Chang, Zhengzhi Zou
May 21, 2020·Oncology Research·Leonard LothsteinTiffany Seagroves
May 22, 2019·Seminars in Cell & Developmental Biology·Tânia CapelôaPierre Sonveaux
Nov 26, 2019·Progress in Biophysics and Molecular Biology·Yang Chang-QingZhang Chen-Yan
Feb 6, 2021·Bioscience Reports·Yomna S Abd El-AzizSumit Sahni

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