The Study Of Ubiquitin Ligase-Fbw7Enhance The Chemosensitivity In Cholangiocarcinoma QBC939

Objective: To investigate the role of Ubiquitin ligase-Fbw7in chemosensitivity ofcholangiocarcinoma cell line(QBC939) in vitro,and to explore its mechanism.Methods: Cell growth inhibition by5-fluorouracil, pharmorubicin, mitomycin,oxaliplatin,and Cisplatin alone, was studied in vitro in human CC cell line(QBC939)by MTT assay.The effect of Fbw7-mediated chemotherapeutic drugs on QBC939cellproliferation were tested. Fbw7overexpression plasmids and siRNA were transfectedby liposome. In addition, to detect Fbw7and p-erk, erk, Bcl-2, Mcl-1, AIB1,PARPexpression by Western Blot.Result:5-fluorouracil, pharmorubicin, mitomycin, oxaliplatin,and Cisplatin treatmentalone inhibited the human CC cell(QBC939),the Inhibitory effect depend on the drugconcentration. Fbw7overexpression suppress the proliferation of QBC939,andinterferenceion promote the proliferation.The effort of chemotherapy drugs onproliferation was enhanced by Fbw7overexpression,but receded by Fbw7interferenceion. The treatment of Cisplatin, epirubicin downregulatedp-erk,erk,Bcl-2,Mcl-1and AIB1protein levels,and Fbw7downregulatedMcl-1andAIB1protein levels.Conclusion: Chemotherapy drugs can effectively inhibit the proliferation ofcholangiocarcinoma cell line(QBC939) at the cellular level,though suppressingBcl-2,Mcl-1and AIB1protein levels,and MAPK Signaling pathway. Fbw7enhancethe effect of chemotherapy drugs on QBC939,which may be associated with AIB1,Mcl-1.