Inhibitory effect of metformin combined with gemcitabine on pancreatic cancer cells in vitro and in vivo

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.