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Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma
Genomic analyses of head and neck squamous cell carcinoma (HNSCC) have highlighted alterations in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, presenting a therapeutic target for multiple ongoing clinical trials with PI3K or PI3K/MTOR inhibitors. However, these inhibitors can potentia...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563873/ https://www.ncbi.nlm.nih.gov/pubmed/32825725 http://dx.doi.org/10.3390/cancers12092371 |
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author | Bernard, Monique Cardin, Guillaume B. Cahuzac, Maxime Ayad, Tareck Bissada, Eric Guertin, Louis Bahig, Houda Nguyen-Tan, Phuc Felix Filion, Edith Ballivy, Olivier Soulieres, Denis Rodier, Francis Christopoulos, Apostolos |
author_facet | Bernard, Monique Cardin, Guillaume B. Cahuzac, Maxime Ayad, Tareck Bissada, Eric Guertin, Louis Bahig, Houda Nguyen-Tan, Phuc Felix Filion, Edith Ballivy, Olivier Soulieres, Denis Rodier, Francis Christopoulos, Apostolos |
author_sort | Bernard, Monique |
collection | PubMed |
description | Genomic analyses of head and neck squamous cell carcinoma (HNSCC) have highlighted alterations in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, presenting a therapeutic target for multiple ongoing clinical trials with PI3K or PI3K/MTOR inhibitors. However, these inhibitors can potentially increase autophagy in HNSCC and indirectly support cancer cell survival. Here, we sought to understand the relationship between the PI3K signaling pathway and autophagy during their dual inhibition in a panel of HNSCC cell lines. We used acridine orange staining, immunoblotting, and tandem sensor Red Fluorescent Protein- Green Fluorescent Protein-, microtubule-associated protein 1 light chain 3 beta (RFP-GFP-LC3B) expression analysis to show that PI3K inhibitors increase autophagosomes in HNSCC cells, but that chloroquine treatment effectively inhibits the autophagy that is induced by PI3K inhibitors. Using the Bliss independence model, we determined that the combination of chloroquine with PI3K inhibitors works in synergy to decrease cancer cell proliferation, independent of the PIK3CA status of the cell line. Our results indicate that a strategy focusing on autophagy inhibition enhances the efficacy of therapeutics already in clinical trials. Our results suggest a broader application for this combination therapy that can be promptly translated to in vivo studies. |
format | Online Article Text |
id | pubmed-7563873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75638732020-10-27 Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma Bernard, Monique Cardin, Guillaume B. Cahuzac, Maxime Ayad, Tareck Bissada, Eric Guertin, Louis Bahig, Houda Nguyen-Tan, Phuc Felix Filion, Edith Ballivy, Olivier Soulieres, Denis Rodier, Francis Christopoulos, Apostolos Cancers (Basel) Article Genomic analyses of head and neck squamous cell carcinoma (HNSCC) have highlighted alterations in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, presenting a therapeutic target for multiple ongoing clinical trials with PI3K or PI3K/MTOR inhibitors. However, these inhibitors can potentially increase autophagy in HNSCC and indirectly support cancer cell survival. Here, we sought to understand the relationship between the PI3K signaling pathway and autophagy during their dual inhibition in a panel of HNSCC cell lines. We used acridine orange staining, immunoblotting, and tandem sensor Red Fluorescent Protein- Green Fluorescent Protein-, microtubule-associated protein 1 light chain 3 beta (RFP-GFP-LC3B) expression analysis to show that PI3K inhibitors increase autophagosomes in HNSCC cells, but that chloroquine treatment effectively inhibits the autophagy that is induced by PI3K inhibitors. Using the Bliss independence model, we determined that the combination of chloroquine with PI3K inhibitors works in synergy to decrease cancer cell proliferation, independent of the PIK3CA status of the cell line. Our results indicate that a strategy focusing on autophagy inhibition enhances the efficacy of therapeutics already in clinical trials. Our results suggest a broader application for this combination therapy that can be promptly translated to in vivo studies. MDPI 2020-08-21 /pmc/articles/PMC7563873/ /pubmed/32825725 http://dx.doi.org/10.3390/cancers12092371 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bernard, Monique Cardin, Guillaume B. Cahuzac, Maxime Ayad, Tareck Bissada, Eric Guertin, Louis Bahig, Houda Nguyen-Tan, Phuc Felix Filion, Edith Ballivy, Olivier Soulieres, Denis Rodier, Francis Christopoulos, Apostolos Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma |
title | Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma |
title_full | Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma |
title_fullStr | Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma |
title_full_unstemmed | Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma |
title_short | Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma |
title_sort | dual inhibition of autophagy and pi3k/akt/mtor pathway as a therapeutic strategy in head and neck squamous cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563873/ https://www.ncbi.nlm.nih.gov/pubmed/32825725 http://dx.doi.org/10.3390/cancers12092371 |
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