Corosolic Acid Inhibits Tumor Growth without Compromising ALPPS-induced Liver Regeneration in Rats

Abstract

BackgroudThe associating liver partition and portal vein ligation (ALPPS) technique is a promising strategy for unresectable tumors without sufficient future liver remnants (FLRs). Criticism has focused on its stimulation of tumor growth. This study explores the effect of corosolic acid (CA) on inhibiting tumor growth without compromising ALPPS-induced liver regeneration and investigates its possible mechanism.MethodsThe ALPPS procedure was performed in Sprague-Dawley rats with orthotopic liver cancer. Blood, tumor and FLR samples in different group were collected.ResultsThe tumor weight in the implantation/ALPPS/CA group was lower than that in the implantation/ALPPS group (p < 0.05). On postoperative day 15, the hepatic regeneration rate and the expression of Ki67+ hepatocytes in the FLRs increased significantly in the group that underwent ALPPS. The number of CD86+ macrophages increased in the FLRs and tumors of the groups that underwent the ALPPS procedure. Additionally, the number of CD206+ macrophages was higher than the number of CD86+ macrophages in the tumors of the implantation group and the implantation/ALPPS group (p < 0.01, respectively); however, the opposite results were observed in the CA groups. The administration of CA downregulated the expression of TGF-β, CD31 and PD-1, whereas it increased the number of CD8+ lymphocytes in tumors.ConclusionsCA inhibits tumor growth without compromising ALPPS-induced liver regeneration. This result may be attributed to the CA-induced downregulation of PD-1 and TGF-β expression and the increased CD8+ lymphocyte infiltration in tumor tissue, associated with the suppression of M2 macrophage polarization.