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The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling

Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to...

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Autores principales: Gu, Jian-Hua, Liu, Cui-Cui, Xie, Jin-Lan, Ma, Bin, Cui, Shao-Min, Yang, Guang-Zhu, He, Shun-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991299/
https://www.ncbi.nlm.nih.gov/pubmed/33777755
http://dx.doi.org/10.3389/fonc.2021.616445
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author Gu, Jian-Hua
Liu, Cui-Cui
Xie, Jin-Lan
Ma, Bin
Cui, Shao-Min
Yang, Guang-Zhu
He, Shun-Cheng
author_facet Gu, Jian-Hua
Liu, Cui-Cui
Xie, Jin-Lan
Ma, Bin
Cui, Shao-Min
Yang, Guang-Zhu
He, Shun-Cheng
author_sort Gu, Jian-Hua
collection PubMed
description Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of bupivacaine on the NSCLC progression. Significantly, we revealed that bupivacaine was able to reduce the proliferation and induce the apoptosis of NSCLC cells. Bupivacaine could attenuate the invasion and migration in the cells. Mechanically, the treatment of bupivacaine increased the expression ratio of light chain 3B-II (LC3B-II)/LC3B-I and the expression of Beclin-1 in the NSCLC cells. Meanwhile, the expression of the autophagic adaptor protein p62 was decreased by bupivacaine treatment in the cells. The treatment of bupivacaine attenuated the phosphorylation of AKT and mTOR in the NSCLC cells. The AKT activator SC79 and autophagy inhibitor 3-methyladenine (3-MA) reversed the bupivacaine-inhibited phosphorylation of AKT and mTOR and bupivacaine-induced autophagy, as well as the bupivacaine-attenuated NSCLC progression in the cells. Bupivacaine could inhibit the tumor growth in vivo. In conclusion, we discovered that the local anesthetic bupivacaine inhibited the progression of NSCLC by inducing autophagy through Akt/mTOR signaling. Our finding provides new insights into the mechanism by which bupivacaine attenuates the development of NSCLC. Bupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC.
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spelling pubmed-79912992021-03-26 The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling Gu, Jian-Hua Liu, Cui-Cui Xie, Jin-Lan Ma, Bin Cui, Shao-Min Yang, Guang-Zhu He, Shun-Cheng Front Oncol Oncology Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of bupivacaine on the NSCLC progression. Significantly, we revealed that bupivacaine was able to reduce the proliferation and induce the apoptosis of NSCLC cells. Bupivacaine could attenuate the invasion and migration in the cells. Mechanically, the treatment of bupivacaine increased the expression ratio of light chain 3B-II (LC3B-II)/LC3B-I and the expression of Beclin-1 in the NSCLC cells. Meanwhile, the expression of the autophagic adaptor protein p62 was decreased by bupivacaine treatment in the cells. The treatment of bupivacaine attenuated the phosphorylation of AKT and mTOR in the NSCLC cells. The AKT activator SC79 and autophagy inhibitor 3-methyladenine (3-MA) reversed the bupivacaine-inhibited phosphorylation of AKT and mTOR and bupivacaine-induced autophagy, as well as the bupivacaine-attenuated NSCLC progression in the cells. Bupivacaine could inhibit the tumor growth in vivo. In conclusion, we discovered that the local anesthetic bupivacaine inhibited the progression of NSCLC by inducing autophagy through Akt/mTOR signaling. Our finding provides new insights into the mechanism by which bupivacaine attenuates the development of NSCLC. Bupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC. Frontiers Media S.A. 2021-03-11 /pmc/articles/PMC7991299/ /pubmed/33777755 http://dx.doi.org/10.3389/fonc.2021.616445 Text en Copyright © 2021 Gu, Liu, Xie, Ma, Cui, Yang and He http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gu, Jian-Hua
Liu, Cui-Cui
Xie, Jin-Lan
Ma, Bin
Cui, Shao-Min
Yang, Guang-Zhu
He, Shun-Cheng
The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling
title The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling
title_full The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling
title_fullStr The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling
title_full_unstemmed The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling
title_short The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling
title_sort local anesthetic bupivacaine inhibits the progression of non-small cell lung cancer by inducing autophagy through akt/mtor signaling
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991299/
https://www.ncbi.nlm.nih.gov/pubmed/33777755
http://dx.doi.org/10.3389/fonc.2021.616445
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