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  Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients

Xiao, Z., Gaertner, S., Morresi-Hauf, A., Genzel, R., Duell, T., Ullrich, A., et al. (2017). Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients. Neoplasia, 19(5), 385-395. doi:10.1016/j.neo.2017.02.011.

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 Creators:
Xiao, Zhiguang1, Author           
Gaertner, Silvia1, Author           
Morresi-Hauf, Alicia2, Author
Genzel, Rebecca2, Author
Duell, Thomas2, Author
Ullrich, Axel1, Author           
Knyazev, Pjotr G.1, Author           
Affiliations:
1Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565172              
2external, ou_persistent22              

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Free keywords: CISPLATIN COMBINATION CHEMOTHERAPY; LUNG-CANCER; IN-VITRO; OVARIAN-CANCER; MELLITUS; INSULIN; TYPE-2; RISK; EGFR; PACLITAXELOncology;
 Abstract: 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 IC50 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.

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Language(s): eng - English
 Dates: 2017
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000401126400001
DOI: 10.1016/j.neo.2017.02.011
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Title: Neoplasia
Source Genre: Journal
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Publ. Info: New York, NY : Stockton Press
Pages: - Volume / Issue: 19 (5) Sequence Number: - Start / End Page: 385 - 395 Identifier: ISSN: 1522-8002
CoNE: https://pure.mpg.de/cone/journals/resource/963017852322