Berberine enhances the therapeutic effect of 5-fluorouracil in Caco-2 colorectal adenocarcinoma cells by alleviating inflammation and inducing apoptosis

Abstract

Purpose: This study aims to investigate whether berberine (BBR) and 5-fluorouracil (5FU), which forms the backbone of chemotherapy, have a synergistic effect on colorectal adenocarcinoma cells (Caco-2) and what mechanisms might be behind this. Materials and Methods: Cell viability was determined by MTT and the combination index (CI) by Chou-Talalay method. Apoptosis and inflammation-related proteins (Bcl-2, p53, IL-6, TNF-α, MMP-9) were measured by ELISA. Results: The IC50 values of BBR and 5FU were found to be 280 µM and 20 mM for 24 h. The combination treatment showed synergistic cytotoxicity, both of which were more pronounced at IC50 (CI=0.143). 5FU+BBR showed a synergistic apoptotic effect by decreasing Bcl-2 and increasing p53 (0.712-fold decrease in Bcl-2 and 2.650-fold increase in p53 compared to 5FU). The increase in IL-6 and TNF-α by 5FU was significantly suppressed by 5FU+BBR (0.733-fold and 0.485-fold). Although there was no significant difference in MMP-9 in 5FU compared to control, 5FU+BBR significantly decreased MMP-9 (0.601-fold). Conclusion: The results show the enormous potential of BBR in combination with 5FU for the chemotherapy of colorectal carcinoma through apoptosis induction, inflammation inhibition and metastasis inhibition.