The Role Of Aldo-Keto Reductase Family 1 Member C1 In Cholangiocarcinoma Occurrence, Development And Mechanism

Objective: Recent years,there are more and more research on tumor metabolism related proteins. Through these studies found that these metabolic enzymes were related to tumorigenesis, development, recurrence and metastasis and many of them have been used as diagnostic tumor markers and therapeutic targets. Gastrointestinal cancer of cholangiocarcinoma refers to the source in the main hepatic duct and extrahepatic bile duct carcinoma. The incidence of cancer accounts for about 3%. The pathogenesis of cholangiocarcinoma is unclear, the occurrence mechanism of in-depth study of bile duct carcinoma, it is possible for cholangiocarcinoma occurrence, development, recurrence and metastasis and provide new ideas, new way for non operation treatment. Aldo-keto reductases(AKRs) superfamily is one of the three enzymes involved in the oxidation-reduction reaction, widely distributed in prokaryotes and eukaryotes. AKRs with triphosphopyridine nucleotide(NADPH) as a coenzyme, involved in a redox reaction. This paper aims to study the AKR1C1(Aldo-keto reductase family 1 member C1) expression in cholangiocarcinoma, and to explore its occurrence, development and metastasis in cholangiocarcinoma in action.Methods: Using cancer tissue microarray and immunohistochemical analysis method to detect the expression of different tumors and adjacent normal tissues of tissue AKR1C1. Real-time PCR to detect the expression of each tumor cell lines AKR1C1, the western blot to detecte the expression of each tumor cell lines and 10 cases of patients with cholangiocarcinoma tissue, adjacent normal tissues AKR1C1 expression.Infection in the cholangiocarcinoma cell strains QBC939 silence AKR1C1 virus plasmid and empty plasmid. CCK-8 assay of cell proliferation in each experimental group. Scratch test and transwell detecting various experimental cell migration. Detected by flow cytometry in each experimental group QBC939 cell cycle arrest and apoptosis. Real-time PCR and Western blot method respectively to detect the experimental QBC939 cell survivin, Bcl- 2, Bax, caspase 3, beta- catenin and E- cadherin mRNA and protein expression.Results: Tissue microarray and immunohistochemical method showed that the expression of AKR1C1 in the cholangiocarcinoma cancer tissue was higher than that in normal tissue. Western blot verification of 10 cases of cholangiocarcinoma tissue and adjacent normal tissue AKR1C1 expression, determined in the AKR1C1 in tumor tissues showed high expression. Real-time PCR and Western blot detected in cholangiocarcinoma cell line QBC939 with high expression of AKR1C1. CCK-8 assay silence AKR1C1 virus infection group and the empty plasmid vector control cell proliferation, cell proliferation silent group was significantly inhibited, and the difference was statistically significant(p <0.05); Detected by flow cytometry results showed that viral infection silence AKR1C1 plasmid group appeared cell cycle arrest, apoptosis increased; Real-time PCR and Western blot method respectively to detect the experimental QBC939 cell survivin, Bcl- 2, Bax, caspase 3, beta- catenin and E- cadherin mRNA and protein expression showed that survivin, caspase 3 and E- cadherin moleculars changes were statistically significant. Proved AKR1C1 is related to the occurrence and development of cholangiocarcinoma and metastasis, but still does not explain the specific pathway, the need to continue to study the subsequent experimental validation.Conclusions: High expression of AKR1C1 in cholangiocarcinoma tissues and QBC939 cells, which are associated with the occurrence, development and metastasis of cholangiocarcinoma cells, may be their participation or indirectly involved in cancer cell growth cycle, apoptosis and metastasis-associated pathway for cholangiocarcinoma research provides new ideas and direction.