Metformin Inhibits Gemcitabine Induced Apoptosis in Pancreatic Cancer Cell Lines.

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.

Analysis of Axin2 expression and function in murine models for pancreatic cancer.

Background: The involvement of Wnt in carcinogenesis and progression of pancreatic cancer is currently intensely discussed. We evaluated activation of the Wnt signaling pathway by using a Wnt reporter mouse strain expressing β-galactosidase under the control of the Axin2 promotor during pancreatitis induced formation of precancerous lesions. We also evaluated activation of Wnt signaling during interaction of pancreatic cancer with the tumor stroma.

Intratumoral heterogeneity of the therapeutical response to gemcitabine and metformin.

Cancer heterogeneity and microenvironmental aspects within a tumor are considered key factors influencing resistance of carcinoma cells to distinct chemotherapeutical agents. We evaluated a high concentration of metformin in combination with gemcitabine on a syngeneic orthotopic mouse model using 6606PDA cells. We observed reduced tumor size and reduced cancer cell proliferation after three weeks of chemotherapy with either compound and noticed an additive effect between gemcitabine and metformin on tumor weight.

Impact of diabetes type II and chronic inflammation on pancreatic cancer.

Background: We explored if known risk factors for pancreatic cancer such as type II diabetes and chronic inflammation, influence the pathophysiology of an established primary tumor in the pancreas and if administration of metformin has an impact on tumor growth.

Methods: Pancreatic carcinomas were assessed in a syngeneic orthotopic pancreas adenocarcinoma model after injection of 6606PDA cells in the pancreas head of either B6.V-Lep(ob/ob) mice exhibiting a type II diabetes-like syndrome or normoglycemic mice.