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The combination of docosahexaenoic acid (DHA) and regorafenib synergistically inhibits colon cancer cell growth.

Utilization of different anticancer agents in combination to produce enhanced inhibitory effects on carcinogenesis is a promising approach to improve anticancer efficacy and reduce potential side‐effects. In this study, we investigated the combination effects between DHA and regorafenib, a potent chemotherapeutic drug for advanced colorectal cancer, on human colon cancer cells. Cell viability assay and colony formation assay demonstrated that the combination of DHA and regorafenib had much stronger inhibitory effects on the cancer cells in comparison to the treatments with DHA or regorafenib alone. These enhanced effects were confirmed to be synergistic by isobologram analysis. Cell cycle and apoptosis assay showed significant G1 phase cell cycle arrest and extensive apoptosis induced by the combination treatment. Results from Western blotting indicated that the inhibitory effects of the combination treatment was associated with increased levels of cleaved caspase 3, cleaved PARP and P21. Overall, our results provide a basis for using DHA and regorafenib in combination for the inhibition of colon cancer. The enhanced anticancer effects by the combination may reduce the required dose of regorafenib for efficacy, which may lower the unwanted side‐effects of regorafenib such as hypertension.