Impact of p53 mutations on the synergistic effects of metformin and radiation on colorectal cancer cells

Abstract

Background Metformin has been reported to be effective as an adjunctive therapy in cancer treatment. In this study, the synergistic effects of metformin and radiotherapy were investigated in colorectal cancer cell lines and colorectal cancer organoids, as were the underlying mechanisms.

Methods This was an experimental study conducted in vitro. Cell proliferation was investigated in vitro after treatment of colorectal cancer cell lines with metformin and radiation. Western blotting was used to analyse treatment-induced changes in p53 expression. The combination index for metformin and irradiation was calculated. Organoids were generated via genomic analysis of colorectal cancer cells from surgical specimens from patients with colorectal cancer. Responses of colorectal cancer organoids with and without p53 mutations to metformin and radiation were compared. Organoids cultured from human colorectal cancer and cell lines were used.

Results In experiments using the colorectal cancer cell lines HCT116 and Lovo, which are p53 wild type cells, the combination treatment of metformin and irradiation appeared to have a synergistic effect. In HCT116 and Lovo cells, metformin treatment increased TP53 expression. No synergistic effect of metformin treatment and irradiation was demonstrated in WiDr and SW620 cells, which contain p53 mutations. Measurements of cell proliferation rates in colorectal cancer organoids also confirmed a similar trend in p53 wild-type organoids and those with p53 mutations.

Conclusion Mutations in the p53 gene in colorectal cancer cells may influence the synergistic effect of metformin and radiotherapy.

Keywords Colorectal cancer, metformin, radiation, organoid, p53

Ann Gastroenterol 2026; 39 (4): 487-494