Hydroxypropyl‑β‑cyclodextrin attenuates the epithelial‑to‑mesenchymal transition via endoplasmic reticulum stress in MDA‑MB‑231 breast cancer cells

Wu,Yifan; Zhao,Yiyang; He,Xuanhong; He,Zhiqiang; Wang,Tian; Wan,Linxi; Chen,Lai; Yan,Nianlong

doi:10.3892/mmr.2019.10802

Hydroxypropyl‑β‑cyclodextrin attenuates the epithelial‑to‑mesenchymal transition via endoplasmic reticulum stress in MDA‑MB‑231 breast cancer cells

Authors:
- Yifan Wu
- Yiyang Zhao
- Xuanhong He
- Zhiqiang He
- Tian Wang
- Linxi Wan
- Lai Chen
- Nianlong Yan
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Laboratory Animal Research Center for Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China
Published online on: November 6, 2019 https://doi.org/10.3892/mmr.2019.10802
Pages: 249-257
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The epithelial‑to‑mesenchymal transition (EMT) has been reported to serve vital roles in regulating the progress of cancer metastasis. In addition, lipid rafts enriched in sphingolipids and cholesterol serve important roles in physiological and biochemical processes as a signaling platform. The present study explored the effects of hydroxypropyl‑β‑cyclodextrin (HP‑β‑CD), a cholesterol‑depleting agent of lipid rafts, on the transforming growth factor (TGF)‑β/Smad signaling pathway and endoplasmic reticulum (ER) stress in mediating EMT in MDA‑MB‑231 breast cancer cells. HP‑β‑CD treatment inhibited TGF‑β1‑induced EMT, based on increased expression of E‑cadherin and decreased expression of vimentin. HP‑β‑CD reduced the expression of the TGF receptor TβRI and blocked the phosphorylation of Smad2. In addition, HP‑β‑CD increased the expression of ER stress‑related proteins (binding immunoglobulin protein and activating transcription factor 6), but TGF‑β1 could reverse these changes. Sodium 4‑phenylbutyrate, an inhibitor of ER stress, suppressed these effects of HP‑β‑CD on EMT and TGF‑β/Smad signaling pathway inhibition in breast cancer cells. Thus, HP‑β‑CD can block the TGF‑β/Smad signaling pathway via diminishing the expression of TβRI which helps to activate ER stress and attenuate EMT in MDA‑MB‑231 cells, highlighting a potential target of lipid rafts for breast cancer treatment.

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