Signal Transduction Pathway And Biological Function Of Interleukin-6 In Cholangiocarcinoma Cell Line QBC939

Cholangiocarcinoma is one of the common neoplasms in the biliary tract,Due to lack of specific symptoms and signs ,its unique biological characteristics and its anatomic features ,it is very difficult to diagnose patients with cholangiocarcinoma in the early stage and resect the tumour radically .Along with its insensitivity to chemotherapy and radiotherapy, the prognosis is still very poor. In recent years cholangiocarcinoma in the crowd to the incidence rate of 5% evry year increase in gastrointestinal tumor is the fastest increase in the tumor, malignant tumors of the hepatobiliary system of 10% to 15%, so it is regarded as crucial to study the carcinogenesis mechanism of cholangiocarcinoma and find new efffective therapeutic approaches of them. Cholangiocarcinoma has confirmed the high-risk factors include congenital malformation biliary anatomy, chronic inflammation, hepatolithiasis, some of the bile duct epithelial carcinogenic substances, as well as the impact of such autoimmune diseases. These are all risk factors for biliary epithelial cells and stimulate a chronic inflammatory, such as damage caused cholestatic the common characteristic of inflammatory cells and bile duct cells may be damaged by the release of cytokines (such as IL-6) and growth factor, as well as the deposition bile acid-induced injury cell gene mutation, the last of normal bile duct cells in the proliferation of change in terms of regulation and control.It's found that interleukin-6 (IL-6) is by far the most widely function of cytokines, can promote a variety of cell proliferation and differentiation. It is more extensive and can be expressed in various cell surface by IL-6 receptor-mediated. IL-6 receptor can be activated through its intracellular signal a series of protein molecules to achieve IL-6 response gene expression induced. It's found that certain tumors (such as colon cancer, liver cancer, ovarian cancer, etc.) in patients with serum levels of IL-6 increased significantly. A recent study found that IL-6 in the incidence of cholangiocarcinoma play an important role in bile duct cells and IL-6 autocrine in human malignant cholangitis, the high expression of IL-6 can contribute to malignant transformation of cell growth and survival, IL -6 can inhibit cell senescence and can enhance the activity of telomerase to extend the survival of cholangiocarcinoma cells. In this process, the JAK family protein tyrosine kinase include the Jak1, Jak2 and Tyk2, signal transduction and transcriptional activation (signal transducers and activators of transcription, STAT) family of Stat3 and Stat1 and various signal protein of Ras signaling pathway, extensive participate in IL-6 in a variety of target cells signal transduction function, and formed a two IL-6 signaling pathways: Ras way and JAK / STAT way. the JAK / STAT pathway compared with Ras studies is later, in recent years ,it has become hot spots of cellular signal transduction research in international .It's not to see IL-6 stimulation with related to the JAK / STAT signaling pathway in cholangiocarcinoma systematically study reported in the country.This experiment carries on the related IL-6 signal conduction function in human cholangiocarcinoma cells, is helpful in expounded that the JAK/ STAT signal pathway the influential role in cholangiocarcinoma pathogenesis, enabled us to have a deeper step understanding in the molecular level to the cholangiocarcinoma pathogenesis, will block specific cytokines and their receptors will become a new kind of treatment. Objective: To investigate the signal pathway of the biological effects of interleukin-6(IL-6) in Cholangiocarcinoma cell line QBC939.Methods :(1)MTT method was used to detect the effect of IL-6 on the growth of QBC939 cells.(2)The electrophoretic mobility shift assay (EMSA) and Western blot were used to detect the activation of the transcription factor Stat3 and protein kinase Jak1 in QBC939 cells by IL-6.(3)The localization of phosphor-Stat3 was determined by immunocytochemistry.Results:(1) IL-6 could remarkably promote the growth of QBC939 cells.(2)Both the transcription factor Stat3 and protein kinase Jak1 were activated by IL-6 in QBC939 cells,and the activity of Stat3 was dependent on dose and time course of IL-6 treatment.(3)The phospho-Stat3 was detected primarily in the nuclei of QBC939 cells.Conclusion:(1) cholangiocarcinoma QBC939 cells in a certain rhuIL-6 stimulating dose range shows that the proliferative response;(2)The proliferation of QBC939 cells in the presence of IL-6 is mediated by the activation of JAK/STAT signal transduction pathway.