IMR Press / FBL / Volume 27 / Issue 4 / DOI: 10.31083/j.fbl2704125
Open Access Original Research
Anti-cancer Drug Anlotinib Promotes Autophagy and Apoptosis in Breast Cancer
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1 Department of Radiation Oncology and Pathology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, 200032 Shanghai, China
2 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai, China
3 Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China
4 Department of Oncology, Shanghai Medical College, Fudan University, 200032 Shanghai, China
5 Shanghai Key Laboratory of Radiation Oncology, 200032 Shanghai, China
*Correspondence: zping@shmu.edu.cn (Ping Zhou); yanghj_1@hotmail.com (Huanjun Yang)
These authors contributed equally.
Academic Editors: Nicholas Pavlidis and Stergios Boussios
Front. Biosci. (Landmark Ed) 2022, 27(4), 125; https://doi.org/10.31083/j.fbl2704125
Submitted: 23 February 2022 | Revised: 19 March 2022 | Accepted: 29 March 2022 | Published: 7 April 2022
(This article belongs to the Special Issue New Insights into Breast Cancer)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Anlotinib, a multi-target tyrosine kinase inhibitor, has significant anti-cancer effects on breast cancer (BC), lung cancer, colon cancer and ovarian cancer, but its mechanism has not been investigated in BC. Methods: The cell viability and growth of human non-triple negative BC cell line MCF-7 and triple negative BC cell line MDA-MB-231 with the treatment of anlotinib were tested by Cell Counting Kit-8 (CCK-8) assay and Ki67 staining. The alteration of genes related to apoptosis and autophagy were investigated by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), western blots and immunocytochemistry (ICC). Cell apoptosis was valued by TUNEL staining and flow cytometry. Further, mouse breast tumour cell lines AT-3 cells were subcutaneously injected into C57BL/6 mice, and the effect of anlotinib intragastrically on tumour growth in vivo was examined. Results: We found that anlotinib suppressed the cell viability and depressed Ki67 staining in MCF-7 and MDA-MB-231 cell lines. Besides, the drug also enhanced cell autophagy and apoptosis of MCF-7 and MDA-MB-231 cell lines, which could be rescued by autophagy inhibitors wortmannin (wort) and 3-methyladenine (3-MA), and BECN1 knockdown. Furthermore, Akt/GSK-3α pathway was inactivated by anlotinib treatment, while rescued by wort, 3-MA and silencing of BECN1 in the MCF-7 or MDA-MB-231 cells. We also found that anlotinib inhibited implanted tumour growth of BC in syngeneic mice. Conclusions: Our study demonstrated that anlotinib inhibited breast cancer cell growth in vitro and in vivo. Anlotinib promoted cell apoptosis and inactivated Akt/GSK-3α pathway of BC cells by inducing cell autophagy. It indicated that anlotinib may be an effective new drug for BC treatment.

Keywords
anlotinib
breast cancer
autophagy
apoptosis
proliferation
Figures
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