Isobavachalcone Sensitizes Cells to E2-Induced Paclitaxel Resistance by Down-Regulating CD44 Expression in ER+ Breast Cancer Cells
Oestrogen receptor (ER) is expressed in approximately 60%‐70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER‐positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER‐negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β‐estradiol (E2)‐induced paclitaxel resistance and that E2 could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E2 could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel‐resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down‐regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel‐resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.
Digital Object Identifier (DOI)
This study was supported by the National Natural Science Foundation of China (Grant No. 81502623), the Natural Science Foundation of Jiangsu Province (BK20150092), the project of Science & Technology of Nanjing (YKK14081) and the Key R & D Special Fund of Jiangsu Province (BE2017611).
Shi, Junfeng; Chen, Yi; Chen, Wenxing; Tang, Cuiju; Zhang, Honghong; Chen, Yuetong; Yang, Xiuwei H.; Xu, Zhi; Wei, Jingsun; and Chen, Jinfei, "Isobavachalcone Sensitizes Cells to E2-Induced Paclitaxel Resistance by Down-Regulating CD44 Expression in ER+ Breast Cancer Cells" (2018). Pharmacology and Nutritional Sciences Faculty Publications. 73.
Medical Nutrition Commons, Medical Pharmacology Commons, Pharmacology, Toxicology and Environmental Health Commons
Published in Journal of Cellular and Molecular Medicine, v. 22, issue 11, p. 5220-5230.
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.