Intratumoral heterogeneity of the therapeutical response to gemcitabine and metformin

• Published in: Oncotarget Vol. 7; no. 35; pp. 56395 - 56407
• Main Authors: Zechner, Dietmar, Bürtin, Florian, Albert, Ann-Christin, Zhang, Xianbin, Kumstel, Simone, Schönrogge, Maria, Graffunder, Josefine, Shih, Hao-Yu, Müller, Sarah, Radecke, Tobias, Jaster, Robert, Vollmar, Brigitte
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 30.08.2016
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Animals; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Blood Glucose; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation - drug effects; Coculture Techniques; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Deoxycytidine - therapeutic use; Drug Resistance, Neoplasm; Gemcitabine; Humans; Hydrogen-Ion Concentration; Male; Metformin - pharmacology; Metformin - therapeutic use; Mice; Mice, Inbred C57BL; Pancreatic Neoplasms; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pancreatic Stellate Cells; Research Paper; Tumor Burden - drug effects; Tumor Microenvironment; Xenograft Model Antitumor Assays; microenvironment; pancreatic adenocarcinoma; syngeneic orthotopic cancer model; chemotherapy; pH Blot

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 66...