Corosolic acid inhibits tumour growth without compromising associating liver partition and portal vein ligation-induced liver regeneration in rats

Abstract

Background Associating liver partition and portal vein ligation (ALPPS) technique is a promising strategy for unresectable primary liver tumours without sufficient future liver remnants (FLRs). Objective Our study explored the effect of corosolic acid (CA) on inhibiting tumour growth without compromising ALPPS-induced liver regeneration. Methods The ALPPS procedure was performed in Sprague–Dawley rats with orthotopic liver cancer. Blood, tumour, and FLR samples were collected, and the effect of CA on the inhibition of tumour progression and ALPPS-induced liver regeneration, and its possible mechanism, were investigated. Results The tumour weight in the implantation/ALPPS group was higher than in the implantation without ALPPS group (p < .05), and the tumour weight in the implantation/ALPPS/CA group was lower than in the implantation/ALPPS group (p < .05). On postoperative day 15, the hepatic regeneration rate, and the expression of Ki67+ hepatocytes in the FLRs had increased significantly in the group that underwent ALPPS. The number of cluster of differentiation (CD) 86+ macrophages markedly increased in the FLRs and in the tumours of groups that underwent the ALPPS procedure. Additionally, the number of CD206+ macrophages was higher than the number of CD86+ macrophages in the tumours of the implantation and the implantation/ALPPS groups (p < .01, respectively); however, the opposite results were observed in the CA groups. The administration of CA downregulated the expression of transforming growth factor-beta (TGF-β), CD31, and programmed cell death protein 1 (PD-1) but increased the number of CD8+ lymphocytes in tumours. Conclusion Corosolic acid inhibits tumour 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 tumour tissue associated with the suppression of M2 macrophage polarisation. Key Messages This study aimed to investigate the effect of CA on ALPPS-induced liver regeneration and hepatic tumour progression after ALPPS-induced liver regeneration. Corosolic acid inhibits tumour 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 tumour tissue associated with the suppression of M2 macrophage polarisation.