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首页> 外文期刊>American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons >Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model.
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Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model.

机译:Rho相关激酶抑制剂可在大鼠肝癌模型中降低肝移植后的肿瘤复发率。

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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.
机译:肝移植术后肝癌复发仍然是肝细胞癌患者的重要问题。小GTPase Rho / Rho相关激酶(ROCK)通路参与癌细胞的运动性和侵袭性。我们调查了他克莫司是否激活Rho / ROCK信号通路来促进大鼠肝癌细胞的侵袭性。我们还研究了在大鼠肝细胞癌模型中实验性肝移植后,ROCK抑制剂Y-27632是否抑制了肿瘤的复发。在肝细胞癌细胞系McA-RH7777的大鼠中进行原位肝移植。将他克莫司施用于肝移植大鼠,并将这些大鼠分为两组:Y-27632处理(10 mg / kg,持续28天)组和Y-27632未处理组。他克莫司增强了癌细胞的迁移并刺激了肌球蛋白轻链(MLC)的磷酸化,肌球蛋白轻链是Rho / ROCK信号的下游效应子。 Y-27632抑制癌细胞迁移和他克莫司诱导的MLC磷酸化。与未经Y-27632治疗的大鼠相比,在经过Y-27632治疗的大鼠中观察到肝移植后肿瘤复发的抑制和生存期的显着延长。他克莫司刺激Rho / ROCK信号通路增强肝细胞癌的侵袭性,ROCK抑制剂Y-27632可作为一种新的抗转移药,用于预防肝移植后肿瘤的复发。

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