The role of RAP1 in graft injury induced cisplatin resistance after liver transplantation

Abstract

BACKGROUND & AIM: Liver transplantation dramatically improved the survival rate of HCC patients. However, tumor recurrence remains a huge threat without any promising curative treatment. We aim to clarify the mechanism of graft injury regulating chemoresistance after liver transplantation. MATERIALS AND METHODS: A rat orthotopic liver transplantation model with liver cancer development was established with applying whole or small-for-size (50%) graft. The expressions of multidrug resistant genes and RAP1 were compared between small and whole graft groups. RAP1 expression was also validated in clinical samples. The role of RAP1 was further explored in vitro and vivo. RESULTS: The expression of RAP1 was constantly higher in liver and tumor in small-for-size group in rat liver transplantation model. (see diagrams) CONCLUSIONS: Overexpression of intragraft RAP1, which upregulated by acute phase liver graft injury, may induce late phase cisplatin resistance after liver transplantation.