FXR expression in a rat model of hilar cholangiocarcinoma

Abstract

Background: To develop a rat model of hilar cholangiocarcinoma and detect Farnesyl X receptor (FXR) expression in hilar cholangiocarcinoma tissues of this model, in order to provide a new method for the treatment of hilar cholangiocarcinoma.Methods: Forty male Wistar rats (body weight, 185 ± 5 g) were randomly divided into two groups (n = 20 each) as follows: The control group was fed a standard diet, and the experimental group was injected by cholangiocarcinoma QBC939 cell suspension along the hilar bile duct into the bile duct bifurcation with microsyringe. Every day note the rats’ mental state, diet, and fur condition. At 4 weeks, one rat of the experimental group was sacrificed, and we recorded changes in hilar bile duct size, texture, and form. This procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma developed only in the experimental group, thereby establishing an experimental model for studying QBC939-induced hilar cholangiocarcinoma. Tumor formation was confirmed by pathological examination, and hilar bile duct tissues were harvested from both the groups. A real-time polymerase chain reaction assay and an immunohistochemical assay were used to analyze the expression of FXR in hilar cholangiocarcinoma and normal hilar bile duct tissues.Results: From the second week, the rats in experimental group began to eat less, and their body mass decreased compared with controls. After 6 weeks, we detected hilar cholangiocarcinoma in 17 rats (85%) in the experimental group. In the experimental group, we found that the levels of total cholesterol, total bilirubin, and direct bilirubin were higher compared with those of the control group. Simultaneously, muddy stones emerged from the bile ducts of rats in the experimental group. The FXR/Gapdh mRNA ratio in hilar cholangiocarcinoma and normal hilar bile duct tissues differed markedly. Light microscopy revealed a granular pattern of FXR expression which reacted with the anti-FXR antibody. Each section was randomly divided into six regions, with 80 cells were observed in every region. Sections with >10% positive cells were designated positive,Sections with <10% positive cells were designated negative. Each group included 4,800 cells. In the experimental group, 1,196 cells (24.9%) were positive and 3,538 cells (73.7%) were positive in the control group, and this difference was statistically significant.Conclusion: FXR expression significantly decreased in hilar cholangiocarcinoma of rats than in those of controls, suggesting that drugs targeting FXR may be a new strategy for hilar cholangiocarcinoma.