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

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-beta), 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-beta 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-beta expression and the increased CD8+ lymphocyte infiltration in tumour tissue associated with the suppression of M2 macrophage polarisation.