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Hirudin inhibits glioma growth through mTOR‐regulated autophagy

Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose‐ and time‐dependen...

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Autores principales: Ma, Ying, Wu, Senbin, Zhao, Fanyi, Li, Huifeng, Li, Qiaohong, Zhang, Jingzhi, Li, Hua, Yuan, Zhongmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494300/
https://www.ncbi.nlm.nih.gov/pubmed/37539490
http://dx.doi.org/10.1111/jcmm.17851
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author Ma, Ying
Wu, Senbin
Zhao, Fanyi
Li, Huifeng
Li, Qiaohong
Zhang, Jingzhi
Li, Hua
Yuan, Zhongmin
author_facet Ma, Ying
Wu, Senbin
Zhao, Fanyi
Li, Huifeng
Li, Qiaohong
Zhang, Jingzhi
Li, Hua
Yuan, Zhongmin
author_sort Ma, Ying
collection PubMed
description Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose‐ and time‐dependently inhibited glioma invasion, migration and proliferation. Mechanistically, hirudin activated LC3‐II but not Caspase‐3 to induce the autophagic death of glioma cells by decreasing the phosphorylation of mTOR and its downstream substrates ULK1, P70S6K and 4EBP1. Furthermore, hirudin inhibited glioma growth and induced changes in autophagy in cell‐derived xenograft (CDX) nude mice, with a decrease in mTOR activity and activation of LC3‐II. Collectively, our results highlight a new anticancer mechanism of hirudin in which hirudin‐induced inhibition of glioma progression through autophagy activation is likely achieved by inhibition of the mTOR signalling pathway, thus providing a molecular basis for hirudin as a potential and effective clinical drug for glioma therapy.
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spelling pubmed-104943002023-09-12 Hirudin inhibits glioma growth through mTOR‐regulated autophagy Ma, Ying Wu, Senbin Zhao, Fanyi Li, Huifeng Li, Qiaohong Zhang, Jingzhi Li, Hua Yuan, Zhongmin J Cell Mol Med Original Articles Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose‐ and time‐dependently inhibited glioma invasion, migration and proliferation. Mechanistically, hirudin activated LC3‐II but not Caspase‐3 to induce the autophagic death of glioma cells by decreasing the phosphorylation of mTOR and its downstream substrates ULK1, P70S6K and 4EBP1. Furthermore, hirudin inhibited glioma growth and induced changes in autophagy in cell‐derived xenograft (CDX) nude mice, with a decrease in mTOR activity and activation of LC3‐II. Collectively, our results highlight a new anticancer mechanism of hirudin in which hirudin‐induced inhibition of glioma progression through autophagy activation is likely achieved by inhibition of the mTOR signalling pathway, thus providing a molecular basis for hirudin as a potential and effective clinical drug for glioma therapy. John Wiley and Sons Inc. 2023-08-04 /pmc/articles/PMC10494300/ /pubmed/37539490 http://dx.doi.org/10.1111/jcmm.17851 Text en © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Ma, Ying
Wu, Senbin
Zhao, Fanyi
Li, Huifeng
Li, Qiaohong
Zhang, Jingzhi
Li, Hua
Yuan, Zhongmin
Hirudin inhibits glioma growth through mTOR‐regulated autophagy
title Hirudin inhibits glioma growth through mTOR‐regulated autophagy
title_full Hirudin inhibits glioma growth through mTOR‐regulated autophagy
title_fullStr Hirudin inhibits glioma growth through mTOR‐regulated autophagy
title_full_unstemmed Hirudin inhibits glioma growth through mTOR‐regulated autophagy
title_short Hirudin inhibits glioma growth through mTOR‐regulated autophagy
title_sort hirudin inhibits glioma growth through mtor‐regulated autophagy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494300/
https://www.ncbi.nlm.nih.gov/pubmed/37539490
http://dx.doi.org/10.1111/jcmm.17851
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