Effect Of NVP-BEZ235 And Sorafenib Combination Of Therapy On Proliferation Of The Human Cholangiocarcinoma Cell Line QBC939 In Virto

Objective: Cholangiocarcinoma is a highly malignant biliary tract tumor,the current treatment is limited,low survival rate.The current study found that many signaling pathways are associated with the development of cholangiocarcinoma and that targeted therapy for cholangiocarcinoma shows potential values.About 90% of patients with cholangiocarcinoma are advanced cancer,so the surgical method can not cure,while cholangiocarcinoma resistance to general chemotherapy is very strong.To evaluate the effect of NVP-BEZ235,in combination with sorafenib on human cholangiocarcinoma(CCA)cell QBC939 proliferation and apoptosis in vitro and aim to find the antiproliferation mechanisms of this effect.Methods: Human CCA cell line QBC939 was used in this study.Cell growth inhibition by NVP-BEZ235 alone for 24 h 48h 72 h,sorafenib alone for 24 h 48h 72 h and both of them for 48 h was studied by MTT assay.Cell apoptosis by NVP-BEZ235 was analyzed using the flow cytometry.Western blotting was used to test anti-apoptotic protein Bcl-2?c-FLIPL ?Mcl-1 and PARP ?Akt?p-Akt?Erk?p-Erk at the same time.Results: NVP-BEZ235 alone had the effect of antiproliferation and induced apoptosis on human CCA cell QBC939,which appeared time-dependent and concentration-dependent effects.NVP-BEZ235 treatment alone inhibited the proliferation.NVPBEZ235 reduced protein expression levels of Mcl-1?c-FLIPL and Bcl-2 and downregulated protein expression level of p-Akt significantly.Sorafenib alone also had the effect of antiproliferation on human CCA cell QBC939,which appeared time-dependent and concentration-dependent effects and downregulated protein expression level of p-Erk significantly.Treatment with NVP-BEZ235 combined with sorafenib exerted synergistic antineoplastic effect on human CCA cell QBC939,which led to a sharp decrease protein expression level in c-FLIPL.Conclusion:NVP-BEZ235 inhibits the phosphorylation of Akt.NVP-BEZ235 downregulates Bcl-2?c-FLIPL?Mcl-1 protein expression level via PI3K/Akt signaling pathway to inhibit the proliferation and induce apoptosis of human CCA cell QBC939.The simultaneous use of NVP-BEZ235 and sorafenib has greater antiproliferative benefit in human CCA cell QBC939 compared to either drug alone,sorafenib increases the NVPBEZ235-induced apoptosis,which probably lies in a sharp decrease protein expression level in c-FLIPL.