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Updated: Jul 17, 2026
The Influence of Liver Resection on Intrahepatic Tumor Growth
Published on: April 9, 2016
Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model
1Second Department of Surgery, Faculty of Medicine, Hirashima University, Hiroshima, Japan.
Abstract:
Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.
Insights
Tacrolimus promotes hepatocellular carcinoma cell invasiveness via the Rho/ROCK pathway. A ROCK inhibitor, Y-27632, suppressed this effect, reducing tumor recurrence after liver transplantation in rats.
Area of Science:
- Oncology
- Transplantation Immunology
- Molecular Biology
Background:
- Tumor recurrence is a significant challenge post-liver transplantation for hepatocellular carcinoma patients.
- The Rho/Rho-associated kinase (ROCK) pathway influences cancer cell motility and invasiveness.
Purpose of the Study:
- To investigate if tacrolimus activates the Rho/ROCK pathway, enhancing hepatocellular carcinoma cell invasiveness.
- To determine if the ROCK inhibitor Y-27632 can prevent tumor recurrence after experimental liver transplantation.
Main Methods:
- Orthotopic liver transplantation in a rat model using McA-RH7777 hepatocellular carcinoma cells.
- Administration of tacrolimus with or without the ROCK inhibitor Y-27632 (10 mg/kg for 28 days).
- Assessment of cancer cell migration, myosin light chain (MLC) phosphorylation, tumor recurrence, and survival rates.
Main Results:
- Tacrolimus increased cancer cell migration and MLC phosphorylation, indicating Rho/ROCK pathway activation.
- Y-27632 inhibited cancer cell migration and tacrolimus-induced MLC phosphorylation.
- Y-27632 treatment significantly suppressed tumor recurrence and prolonged survival in transplanted rats.
Conclusions:
- Tacrolimus stimulates the Rho/ROCK pathway, increasing hepatocellular carcinoma invasiveness.
- The ROCK inhibitor Y-27632 demonstrates potential as an antimetastatic agent to prevent tumor recurrence post-liver transplantation.
