title: Inhibitory effect of metformin combined with gemcitabine on pancreatic cancer cells in vitro and in vivo.
abstract: Pancreatic cancer is a malignant digestive system tumor with a particularly poor prognosis, and is the fourth leading cause of cancer‑associated mortality in the USA. The anti‑diabetic therapeutic agent, metformin (MET) has been demonstrated to exert anti‑tumor effects. The present study assessed the ability of MET, alone or in combination with gemcitabine (GEM), to inhibit the growth of the human CFPAC‑1 pancreatic cancer cell line in vitro and in vivo. Cell counting kit‑8 assays were performed to measure CFPAC‑1 cell viability and apoptosis was detected with annexin V/propidium iodide. Cell cycle analysis was conducted by flow cytometry. The mRNA and protein levels of B‑cell lymphoma‑extra large (Bcl‑xL), Bcl2 associated X protein (Bax), caspase‑3, survivin and cyclin D1 in CFPAC‑1 cells and tumor tissues were detected by reverse transcription‑polymerase chain reaction and western blotting, respectively. Furthermore, the expression levels of caspase‑3 and proliferating cell nuclear antigen in tumor tissues were detected by immunohistochemistry. The results demonstrated that following MET treatment, the growth of CFPAC‑1 cells and xenografts in nude mice was inhibited, the expression levels of Bcl‑xL, survivin and cyclin D1 were downregulated, while the expression levels of Bax and caspase‑3 were upregulated. These effects were enhanced when MET was administered in combination with GEM. The mechanism underlying the anti‑tumor effect of MET may be associated with the induction of cell apoptosis and the inhibition of proliferation.
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Yuqi
authors: Y
authors: Shi
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Zhilong
authors: Z
authors: He
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Zhenyu
authors: Z
authors: Jia
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Chunfang
authors: C
authors: Xu
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D008819:Mice, Nude; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D007004:Hypoglycemic Agents; D003841:Deoxycytidine; D008687:Metformin; D000093542:Gemcitabine