Abstract

Background

Colorectal cancer (CRC) is one of the most common of cancer in the world. Chemotherapy is a standard treatment for cancer, usually used to improve the survival rate of patients. FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) is one of the most important regimen for CRC patients. Previous studies had found that metformin is not only for controlling blood sugar level, but also have antitumor effects. Therefore, we hypothesize that metformin could enhance the therapeutic effect of FOLFOX in inhibiting the growth of CRC cells.

Method

In vitro, we identified the synergistic effect of metformin plus FOLFOX by functional assays including cell proliferation, migration, cell cycle and apoptosis and also analyze the target protein by using Western blot. In Vivo, seven weeks-old male BALB/c nude mice were randomly divided into four groups. The dosage and schedule of metformin and FOLFOX administration were followed by previously published studies.

Results

In vitro, we confirmed that metformin plus FOLFOX group could induce apoptosis significantly compared with FOLFOX only or metformin only group. However, no synergistic effect of metformin and FOLFOX was found in cell migration. In vivo, the metformin plus FOLFOX group had a prominent decrease of tumor volume or weight than FOLFOX-only group and metformin-only group.

Conclusion

These finding suggest that metformin plus FOLFOX could synergistically inhibit CRC cell growth in vitro and in vivo, and the further clinical implication needs to be further validated.