Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer
Authors Wang Y, Liu Y, Du X, Ma H, Yao J
Received 9 December 2019
Accepted for publication 20 February 2020
Published 4 March 2020 Volume 2020:13 Pages 1909—1919
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Takuya Aoki
Ye Wang,* Yanfang Liu,* Xinyang Du, Hong Ma, Jing Yao
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jing Yao
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1277, Wuhan, Hubei Province 430022, People’s Republic of China
Tel +86-189 8627 1157
Purpose: Berberine (BBR), a traditional Chinese medicine, has been shown effects on inhibiting cancer development. Autophagy-mediated resistance plays an important role in cancer progression; therefore, regulation of autophagy is a novel therapeutic strategy for cancer treatment. However, effects of BBR on autophagy-mediated resistance have not been reported.
Methods: MCF-7 breast cancer cells and the doxorubicin (ADR)-resistant MCF-7 cells (MCF-7/ADR) were used for analyses. Western blotting was conducted to evaluate protein expression; MTT, colony formation, and EdU assays were conducted to assess cell proliferation; transmission electron microscopy was used to monitor autophagy levels; and a xenograft tumor model was established to assess the effects of BBR on reversing doxorubicin resistance.
Results: We confirmed that BBR, recently identified as a suppressor of autophagy, inhibits autophagosome formation in MCF-7/ADR cells. Treatment with BBR blocked the accumulation of the autophagy-associated protein LC3II, resulting in cellular accumulation of p62, reduced cell proliferation, and reversal of doxorubicin resistance. Mechanistically, we found that BBR inhibited autophagy by modulating the PTEN/Akt/mTOR signaling pathway. In vivo, our study showed that BBR exerts clear anti-tumor effects.
Conclusion: The results of this study suggest that BBR reverses doxorubicin resistance in breast cancer cells by inhibiting autophagy. This finding highlights the potential clinical application of BBR in the treatment of breast cancer.
Keywords: breast cancer, berberine, chemoresistance, PTEN, autophagy, ADR
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]