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The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells
Trastuzumab emtansine (T-DM1), an antibody–drug conjugate (ADC) of trastuzumab and cytotoxic agent emtansine (DM1), has been approved for the therapy of metastatic HER2-positive breast cancer after prior treatment of trastuzumab and taxane. The impressive efficacy exhibited by T-DM1 has heightened t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270446/ https://www.ncbi.nlm.nih.gov/pubmed/32495214 http://dx.doi.org/10.1186/s13568-020-01044-0 |
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author | Liu, Peipei Fan, Jiajun Wang, Ziyu Zai, Wenjing Song, Ping Li, Yongping Ju, Dianwen |
author_facet | Liu, Peipei Fan, Jiajun Wang, Ziyu Zai, Wenjing Song, Ping Li, Yongping Ju, Dianwen |
author_sort | Liu, Peipei |
collection | PubMed |
description | Trastuzumab emtansine (T-DM1), an antibody–drug conjugate (ADC) of trastuzumab and cytotoxic agent emtansine (DM1), has been approved for the therapy of metastatic HER2-positive breast cancer after prior treatment of trastuzumab and taxane. The impressive efficacy exhibited by T-DM1 has heightened the need for more further studies on the underlying mechanisms of T-DM1 cytotoxicity. Previous research suggested that autophagy was crucial for cancer therapy, but the role of autophagy in T-DM1 treatment has not been investigated. Here, we demonstrated for the first time that T-DM1 triggered obvious autophagy in HER2-positive SK-BR-3 and BT-474 breast cancer cells. Blocking autophagy with pharmacological inhibitors chloroquine (CQ) or LY294002 partly reduced T-DM1-induced apoptosis and Caspase-3/7 activation, suggesting that autophagy played an essential role in the cytotoxicity induced by T-DM1 in HER2-positive breast cancer cells. Further investigation demonstrated that Akt/mTOR signaling pathway was involved in T-DM1-induced autophagy in a time-dependent manner. Altogether, our results highlighted the important role of autophagy as a novel mechanism for T-DM1-induced cytotoxicity and elucidated the critical relationships between T-DM1-induced autophagy and apoptosis in human HER2-positive breast cancer cells, which provides novel insight into the underlying anti-tumor mechanism of T-DM1. |
format | Online Article Text |
id | pubmed-7270446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-72704462020-06-15 The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells Liu, Peipei Fan, Jiajun Wang, Ziyu Zai, Wenjing Song, Ping Li, Yongping Ju, Dianwen AMB Express Original Article Trastuzumab emtansine (T-DM1), an antibody–drug conjugate (ADC) of trastuzumab and cytotoxic agent emtansine (DM1), has been approved for the therapy of metastatic HER2-positive breast cancer after prior treatment of trastuzumab and taxane. The impressive efficacy exhibited by T-DM1 has heightened the need for more further studies on the underlying mechanisms of T-DM1 cytotoxicity. Previous research suggested that autophagy was crucial for cancer therapy, but the role of autophagy in T-DM1 treatment has not been investigated. Here, we demonstrated for the first time that T-DM1 triggered obvious autophagy in HER2-positive SK-BR-3 and BT-474 breast cancer cells. Blocking autophagy with pharmacological inhibitors chloroquine (CQ) or LY294002 partly reduced T-DM1-induced apoptosis and Caspase-3/7 activation, suggesting that autophagy played an essential role in the cytotoxicity induced by T-DM1 in HER2-positive breast cancer cells. Further investigation demonstrated that Akt/mTOR signaling pathway was involved in T-DM1-induced autophagy in a time-dependent manner. Altogether, our results highlighted the important role of autophagy as a novel mechanism for T-DM1-induced cytotoxicity and elucidated the critical relationships between T-DM1-induced autophagy and apoptosis in human HER2-positive breast cancer cells, which provides novel insight into the underlying anti-tumor mechanism of T-DM1. Springer Berlin Heidelberg 2020-06-03 /pmc/articles/PMC7270446/ /pubmed/32495214 http://dx.doi.org/10.1186/s13568-020-01044-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Liu, Peipei Fan, Jiajun Wang, Ziyu Zai, Wenjing Song, Ping Li, Yongping Ju, Dianwen The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells |
title | The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells |
title_full | The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells |
title_fullStr | The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells |
title_full_unstemmed | The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells |
title_short | The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells |
title_sort | role of autophagy in the cytotoxicity induced by trastuzumab emtansine (t-dm1) in her2-positive breast cancer cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270446/ https://www.ncbi.nlm.nih.gov/pubmed/32495214 http://dx.doi.org/10.1186/s13568-020-01044-0 |
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