Avasimibe interrupts cholangiocarcinoma induced by thioacetamide in rats / 第二军医大学学报

ABSTRACT

Objective To explore the effect of avasimibe in preventing cholangiocarcinoma induced by thioacetamide, a chemical carcinogen. Methods Male SD rats were given drinking water containing 300 mg/L thioacetamide and stopped drinking after 3 months, and then were divided into two groups (n=5) control group and avasimibe intervention group. The control group was given normal drinking water, while the avasimibe intervention group was given drinking water containing avasimibe (30 mg/kg) by gavage. After 3 months of intervention, all rats were sacrificed and liver lesions were observed by hematoxylin-eosin (H-E) staining. The expression of aldo-keto reductase family 1 member C1 (AKR1C1) and Ki-67 in liver lesions of rats was detected by immunohistochemical staining. Meanwhile, different concentrations (0, 10, 20 μmol/L) of avasimibe were used to treat the cholangiocarcinoma cell line QBC939, the cell proliferation ability was detected by cell counting kit 8 (CCK-8) assay, and the expression of AKR1C1 in QBC939 cells was detected by qRT-PCR and Western blotting. Results The results of H-E staining showed that all rats in the control group developed visible tumors under the microscope, and the tumor formation rate was 100% (5/5), while only one rat in the avasimibe intervention group developed tumors, with a 20% (1/5) tumor formation rate. The results of immunohistochemistry showed that the expression levels of AKR1C1Ki-67 in liver lesions of rats in the avasimibe intervention group were significantly lower than those in the control group (P<0.05, P<0.01). The results of CCK-8 assay showed that avasimibe significantly inhibited the proliferation of QBC939 cells. The results of qRT-PCR and Western blotting showed that the expression levels of AKR1C1 mRNA and protein in QBC939 cells after the intervention of avasimibe were significantly decreased compared with those of the control group (both P<0.01). Conclusion Avasimibe can interrupt the occurrence of intrahepatic cholangiocarcinoma caused by chemical carcinogens and is a potential drug for preventing cholangiocarcinoma. AKR1C1 might be a potential therapeutic target of cholangiocarcinoma..