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Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients
The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Neoplasia Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384889/ https://www.ncbi.nlm.nih.gov/pubmed/28391030 http://dx.doi.org/10.1016/j.neo.2017.02.011 |
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author | Xiao, Zhiguang Gaertner, Silvia Morresi-Hauf, Alicia Genzel, Rebecca Duell, Thomas Ullrich, Axel Knyazev, Pjotr G. |
author_facet | Xiao, Zhiguang Gaertner, Silvia Morresi-Hauf, Alicia Genzel, Rebecca Duell, Thomas Ullrich, Axel Knyazev, Pjotr G. |
author_sort | Xiao, Zhiguang |
collection | PubMed |
description | The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background. EGFR downstream signaling evaluation further demonstrated that metformin, at its IC(50) value, modified apoptosis caused in erlotinib or chemotherapeutic agent-treated cells via AKT activation and the inhibition of caspase 3 and PARP cleavages. These regulations were driven independently from EGFR, LKB1, KRAS, PTEN and p53 status. Metformin triggered autophagy (LC3B expression) was identified to interplay with apoptosis to attenuate the drug effect and postpone cancer cell death. In the retrospective study of 8 NSCLC patients, the administration of metformin did not induce statistically significant changes as assessed by immunohistochemical staining of pERK, pAKT and cleaved PARP. Consequently, the application of metformin for T2D NSCLC patients receiving chemo or EGFR targeted therapy should be considered with caution. |
format | Online Article Text |
id | pubmed-5384889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53848892017-04-14 Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients Xiao, Zhiguang Gaertner, Silvia Morresi-Hauf, Alicia Genzel, Rebecca Duell, Thomas Ullrich, Axel Knyazev, Pjotr G. Neoplasia Original article The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background. EGFR downstream signaling evaluation further demonstrated that metformin, at its IC(50) value, modified apoptosis caused in erlotinib or chemotherapeutic agent-treated cells via AKT activation and the inhibition of caspase 3 and PARP cleavages. These regulations were driven independently from EGFR, LKB1, KRAS, PTEN and p53 status. Metformin triggered autophagy (LC3B expression) was identified to interplay with apoptosis to attenuate the drug effect and postpone cancer cell death. In the retrospective study of 8 NSCLC patients, the administration of metformin did not induce statistically significant changes as assessed by immunohistochemical staining of pERK, pAKT and cleaved PARP. Consequently, the application of metformin for T2D NSCLC patients receiving chemo or EGFR targeted therapy should be considered with caution. Neoplasia Press 2017-04-07 /pmc/articles/PMC5384889/ /pubmed/28391030 http://dx.doi.org/10.1016/j.neo.2017.02.011 Text en © 2017 Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Xiao, Zhiguang Gaertner, Silvia Morresi-Hauf, Alicia Genzel, Rebecca Duell, Thomas Ullrich, Axel Knyazev, Pjotr G. Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients |
title | Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients |
title_full | Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients |
title_fullStr | Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients |
title_full_unstemmed | Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients |
title_short | Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients |
title_sort | metformin triggers autophagy to attenuate drug-induced apoptosis in nsclc cells, with minor effects on tumors of diabetic patients |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384889/ https://www.ncbi.nlm.nih.gov/pubmed/28391030 http://dx.doi.org/10.1016/j.neo.2017.02.011 |
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