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Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma
BACKGROUND: New and effective chemotherapy or targeted therapy strategies are needed against laryngeal squamous cell carcinoma (LSCC). We aimed to explore the antitumor effect of dual PI3K/mTOR inhibitor combined with autophagy suppression on LSCC and its underlying mechanism. METHODS: Hep-2 and AMC...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189222/ https://www.ncbi.nlm.nih.gov/pubmed/35706786 http://dx.doi.org/10.21037/tcr-21-2325 |
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author | Huang, Hui-Ying Li, Ke-Nan Lau, Hui-Ching Hsueh, Chi-Yao Cong, Ning Zhang, Ming |
author_facet | Huang, Hui-Ying Li, Ke-Nan Lau, Hui-Ching Hsueh, Chi-Yao Cong, Ning Zhang, Ming |
author_sort | Huang, Hui-Ying |
collection | PubMed |
description | BACKGROUND: New and effective chemotherapy or targeted therapy strategies are needed against laryngeal squamous cell carcinoma (LSCC). We aimed to explore the antitumor effect of dual PI3K/mTOR inhibitor combined with autophagy suppression on LSCC and its underlying mechanism. METHODS: Hep-2 and AMC-HN-8 cell lines were treated with the Akt inhibitor LY294002, mTOR inhibitor rapamycin, and dual inhibitor NVP-BEZ235 separately. The biological characteristics of in vitro proliferation, cell cycle, apoptosis, migration, invasion, and autophagy were analyzed, and the expression levels of PI3K/Akt/mTOR pathway-related proteins were also measured. The in vivo effects of NVP-BEZ235 combined with inhibition of autophagy using pharmacological inhibitor was further assessed. RESULTS: Compared with Akt or mTOR inhibitor, NVP-BEZ235 had the most significant biological effects on LSCC cells. When combined with various autophagy inhibitors, along with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC through increasing cell apoptosis and death both in vitro and vivo. CONCLUSIONS: NVP-BEZ235 exerted potent antitumor effects on LSCC, especially when combined with the autophagy inhibitor both in vitro and vivo, providing convincing experimental data for new molecular targeted therapy for LSCC. |
format | Online Article Text |
id | pubmed-9189222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-91892222022-06-14 Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma Huang, Hui-Ying Li, Ke-Nan Lau, Hui-Ching Hsueh, Chi-Yao Cong, Ning Zhang, Ming Transl Cancer Res Original Article BACKGROUND: New and effective chemotherapy or targeted therapy strategies are needed against laryngeal squamous cell carcinoma (LSCC). We aimed to explore the antitumor effect of dual PI3K/mTOR inhibitor combined with autophagy suppression on LSCC and its underlying mechanism. METHODS: Hep-2 and AMC-HN-8 cell lines were treated with the Akt inhibitor LY294002, mTOR inhibitor rapamycin, and dual inhibitor NVP-BEZ235 separately. The biological characteristics of in vitro proliferation, cell cycle, apoptosis, migration, invasion, and autophagy were analyzed, and the expression levels of PI3K/Akt/mTOR pathway-related proteins were also measured. The in vivo effects of NVP-BEZ235 combined with inhibition of autophagy using pharmacological inhibitor was further assessed. RESULTS: Compared with Akt or mTOR inhibitor, NVP-BEZ235 had the most significant biological effects on LSCC cells. When combined with various autophagy inhibitors, along with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC through increasing cell apoptosis and death both in vitro and vivo. CONCLUSIONS: NVP-BEZ235 exerted potent antitumor effects on LSCC, especially when combined with the autophagy inhibitor both in vitro and vivo, providing convincing experimental data for new molecular targeted therapy for LSCC. AME Publishing Company 2022-05 /pmc/articles/PMC9189222/ /pubmed/35706786 http://dx.doi.org/10.21037/tcr-21-2325 Text en 2022 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Original Article Huang, Hui-Ying Li, Ke-Nan Lau, Hui-Ching Hsueh, Chi-Yao Cong, Ning Zhang, Ming Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
title | Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
title_full | Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
title_fullStr | Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
title_full_unstemmed | Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
title_short | Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
title_sort | dual inhibition of autophagy and pi3k/mtor pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189222/ https://www.ncbi.nlm.nih.gov/pubmed/35706786 http://dx.doi.org/10.21037/tcr-21-2325 |
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