Study On The Regulation Of FBXW7-HIF1? Signaling Pathway In Hilar Cholangiocarcinoma

Cholangiocarcinoma is a malignant tumor arising from bile duct epithelial cells.It is the most common tumor of hepatobiliary system except liver cancer.According to anatomical position,it can be divided into intrahepatic cholangiocarcinoma,hilar cholangiocarcinoma and distal cholangiocarcinoma.Hilar Cholangiocarcinoma(HCC)occurs in the left and right hepatic duct and common hepatic duct,accounting for more than 50%of the incidence of cholangiocarcinoma.In recent years,the morbidity and mortality of HCC in China has been on the rise.The cause of the disease is not clear,and there is no effective screening and early diagnosis method.HCC patients were mostly asymptomatic in early stage.HCC is characterized by strong tumor invasiveness and early metastasis.Most patients with atypical symptoms such as yellow staining of the skin and mucous membrane and pain in the upper abdomen had advanced tumors.They lost the chance of surgery.Existing studies have demonstrated that HCC is not sensitive to radiotherapy or chemotherapy,the commonly used chemotherapy regiments do not significantly improve the prognosis of HCC patients.Surgical resection is currently the only effective method for the treatment of HCC.HCC is aggressive and has early metastasis.As a result,the surgical resection rate is low,the prognosis is poor,and the postoperative recurrence rate is high.Even in early HCC cases,the operative efficiency was not satisfactory.The clinical efficacy of HCC is still not ideal.Further study of the tumor biological characteristics of HCC and search for new early diagnosis and treatment targets are of great importance to improve the prognosis and prolong the survival of patients.PurposeTo investigate the expression of FBXW7-HIF-1?signal pathway in hilar cholangiocarcinoma and its clinical significance.To study the role of GSK 3,an inhibitor,in the regulation of FBXW7-HIF-1? signal pathway in hilar cholangiocarcinoma.Materials and MethodsThe paraffin blocks of hilar cholangiocarcinoma(39 cases)and paracancerous tissue(9 cases)were selected.The expression of FBXW 7 in the two tissues was detected by Western blot and immunohistochemistry,and the relationship between the expression and the clinicopathological characteristics of hilar cholangiocarcinoma was analyzed.The expression of FBXW 7 in human normal bile duct epithelial cell line HIBEpic and hilar cholangiocarcinoma cell line QBC939 were detected by Western blot.Western blot was used to detect the expression of HIF-1?protein in the stable transfected cell lines with high and low expression of FBXW 7.QBC939 cells with high and low expression of FBXW 7 were injected subcutaneously into nude mice and treated with GSK 3 to verify the effect on tumor growth.ResultsThe expression of FBXW 7 in QBC939 cell line was significantly lower than that in HIBEpic cell line.FBXW7 expression was significantly correlated with TNM stage and metastasis of hilar cholangiocarcinoma.HIF-1? protein expression was significantly decreased in FBXW 7 highly expressed cell lines.GSK 3 treatment inhibited tumor growth.ConclusionFBXW 7 can inhibit the growth of hilar cholangiocarcinoma.GSK 3 can inhibit the expression of HIF-1 a by regulating the signal pathway of FBXW 7-HIF-1?.