Short-term cardiotrophin-1 (CT-1) rescues marginalcirrhotic liver remnant after major hepatectomywithout increasing the risk of tumor recurrence

Abstract

Background Hepatic resection is not applicable to the majority ofhepatocellular carcinoma (HCC) patients due to insufficient liverfunction reserve. Cardiotrophin-1 (CT-1), a member of the inter-leukin-6 family, has demonstrated protective and pro-proliferativeeffects in the myocytes and hepatocytes.Aim The present study aimed to investigate the potential role ofCT-1 in rescuing marginal cirrhotic liver remnant in a rat orthotopicHCC model.Materials and Methods Liver cirrhosis was induced by subcuta-neous injection of CCL4 for 8 weeks. The rat orthotopic HCC model was generated by injecting HCC cells into the left lobe of the liver.Animals received the following treatments: 1) hepatectomy only, n =6; 2) CT-1 (2 µg/kg) intraportal vein injection (i.pv) right after hepa-tectomy, n = 6; 3) CT-1 (2 µg/kg) i.pv right after hepatectomy, and 1µg/kg intraperitoneal injection (i.p) 24 hr after hepatectomy, n = 6; 4)CT-1 (2 µg/kg) i.p 24 hr before hepatectomy, n = 6; 5) CT-1 (2 µg/kg)i.p 24 hr before hepatectomy, and 1 µg/kg i.p 24 hr after hepatectomy,n = 6.Results The double-dose CT-1 significantly improved animal survival, and all the surviving animals did not present with tumorrecurrence. CT-1 administration decreased the plasma AST and ALT levels, augmented the number of Ki-67+and gp130+cells, andrestored the ATP levels. CT-1 culture enhanced the viability of pri-marily isolated hepatocytes. CT-1 treatment increased the expressionof Akt and PI3K in the liver remnant.Conclusions A short-term administration of CT-1 could improveanimal survival after major hepatectomy, through promoting cell pro-liferation and restoring cell survival.