Oleanolic acid enhanced the anticancer effect of fluorouracil by regulating Ca2+ levels in hepatocellular carcinoma cells

Oleanolic acid (OA) is recognized for its anticancer properties, which are similar to those of conventional chemotherapeutic agents used in clinical practice. However, its role in modulating the sensitivity of cancer cells to fluorouracil (5FU) has not yet been documented. This study aimed to examine the effects of OA and 5FU co-administration on hepatocellular carcinoma (HCC) and uncover the mechanisms involved. In this study, the efficacy of combination therapy with OA and 5FU in treating HCC was evaluated using the MTT cell proliferation assay, plate clone formation assay, Hoechst 33342 staining, western blot assay, and Ca2+ fluorescence probe. The results demonstrated that compared with the use of OA or 5FU alone, OA and 5FU combination therapy significantly inhibited the proliferation of HEPG2 cells and enhanced cell apoptosis and Ca2+ levels in HCC. Additionally, the inhibitory effect of OA and 5FU combination therapy on cell proliferation and apoptosis was partially reversed by the calcium channel blocker 2-aminoethyldiphenyl borate (2-APB). In summary, these findings indicated that synergistic treatment with OA and 5FU can enhance cell apoptosis, inhibit cell proliferation, and regulate Ca2+ signaling in HCC, providing new guidance for the clinical treatment of HCC.