Metformin Inhibits Gemcitabine Induced Apoptosis in Pancreatic Cancer Cell Lines.

Abstract:

:Many preclinical and clinical studies are currently evaluating metformin in combination with classical therapeutic agents as anti-cancer therapy. In this study we used three distinct pancreatic cancer cell lines and evaluated cell death by trypan blue assay and Western Blots using antibodies directed against cleaved caspase 3 and PARP. Surprisingly, we observed that 20mM metformin did not enhance, but rather inhibited gemcitabine induced cell death in murine 7265PDA, 6606PDA and 6606l cells. Microenvironmental aspects such as oxygen supply or the pH value did not influence the inhibition of cancer cell apoptosis by metformin. Glucose concentration in the medium, however, had a major effect on the impact of metformin. Medium with 0.5g/L glucose strongly increased metformin induced apoptosis and also prevented the inhibitory effect of metformin on gemcitabine induced cell apoptosis, when compared with medium containing 4.5g/L glucose. We conclude that the combination of metformin with gemcitabine has inappropriate effects for a successful treatment of pancreatic cancer. Thus, it might be more promising to use metformin in combination with other drugs that reduce the uptake or the metabolism of glucose.

journal_name

J Cancer

journal_title

Journal of Cancer

authors

Zechner D,Albert AC,Bürtin F,Vollmar B

doi

10.7150/jca.17972

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

1744-1749

issue

10

issn

1837-9664

pii

jcav08p1744

journal_volume

8

pub_type

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