FXR expression in rats of hilar cholangiocarcinoma

• Published in: Scientific reports Vol. 12; no. 1; pp. 8741 - 7
• Main Authors: Zhang, Meng-yu, Luo, Ming, Wang, Jie-ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/699/67; 692/699/67/70; Alanine; Alanine transaminase; Animal models; Animals; Aspartate transaminase; Bile Duct Neoplasms - pathology; Bile ducts; Bile Ducts, Intrahepatic - pathology; Cholangiocarcinoma; Cholangiocarcinoma - pathology; Drug delivery; Drug development; Gene therapy; Glyceraldehyde-3-phosphate dehydrogenase; Humanities and Social Sciences; Immunohistochemistry; Klatskin Tumor - genetics; Klatskin Tumor - pathology; Male; mRNA; multidisciplinary; Physical activity; Polymerase chain reaction; Rats; Rats, Wistar; Rodents; Science; Science (multidisciplinary); Therapeutic targets; Transaminase; Tumors
• DOI: 10.1038/s41598-022-12850-w
• ISSN: 2045-2322

The study objective was to detect the expression of farnesoid X receptor (FXR) in a rat model of hilar cholangiocarcinoma to provide a new therapeutic target for gene therapy in hilar cholangiocarcinoma. Sixty male Wistar rats (weighing 190 ± 8 g) were randomly divided into three groups (experimental group, control group and sham operation group, 20 rats in each group). The three groups were fed a standard diet. The QBC939 cell suspension of cholangiocarcinoma was injected into the hilar bile duct in the experimental group with a microsyringe. The control group was injected with normal saline, and the sham operation group was not injected with any drugs. A modified tail suspension test (TST) was used to evaluate the mental state and physical activity of rats every day. At 5 weeks, one rat in the experimental group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at one and half months. After one and half months, hilar cholangiocarcinoma only occurred in the experimental group. Pathological examination confirmed the formation of tumours, and hilar bile duct tissues were taken from the three groups. FXR expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT–PCR) and immunohistochemistry. After two weeks, the rats in the experimental group ate less, and their weight was significantly reduced. One and half months later, hilar cholangiocarcinoma was detected in 16 rats in the experimental group. The levels of alanine aminotransferase and aspartate transaminase in the experimental group were higher than those in the other two groups. The ratio of FXR/GAPDH mRNA was significantly different among the hilar cholangiocarcinoma, control and sham operation groups. Under the light microscope, FXR protein reacted with anti-FXR antibody and showed granular expression. Every pathological section included 4800 cells. A total of 1856 positive cells were in the experimental group, 3279 positive cells were in the control group, and 3371 positive cells were in the sham operation group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues, suggesting that drugs targeting FXR may be a new strategy for the treatment of hilar cholangiocarcinoma.