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-alpha, MMP-9) were measured by ELISA. Results: The IC50 values of BBR and 5FU were found to be 280 mu M 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-alpha 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.