A Synergistic Combination of Oleanolic Acid and Apatinib to Enhance Anti-tumor Effect on Liver Cancer Cells and Protect against Hepatic Injury

Background: As a pentacyclic triterpenoid, OA (oleanolic acid) has exhibited anti-inflammatory, immunomodulatory and antitumor effects. VEGFR-2 (vascular endothelial cells receptor-2) tyrosine kinase activity could be inhibited by apatinib, a small-molecule anti-angiogenic agent.Objective: Thus, this study sought to investigate the mechanism underlying the synergistic anti-tumor activity of combined OA and apatinib patent.Methods: Through CCK8 (Cell counting kit 8 assay), flow cytometric and western blotting techniques, we conducted in vitro studies on apatinib and OA effects on cell proliferation and apoptosis in H22 cell line. H22 tumor-burdened mice model was established in vivo, while the related signaling pathways were studied via pathological examination, western blotting and qPCR (quantitative polymerase chain reaction).Results: Growth of H22 cells in vitro and in vivo could be inhibited effectively by apatinib and OA. Thus, OA repaired liver function and inhibited oxidative stress induced by apatinib.Conclusion: OA can treat apatinib induced liver injury in H22 Tumor-burdened mice by enhancing the suppresssive effect of apatinib on the growth of tumor.