| Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor which arises from the epithelial cells of intrahepatic bile ducts (beyond the second order bile ducts), and it has a global increasing trend in recent years. ICC is the second most common primary liver malignancy after hepatocellular carcinoma (HCC), accounting for10%to15%of all primary liver cancers. From1972to1994, cholangiocarcinoma was the most rapidly increasing malignancy in Shanghai, with an increase in incidence of119%in men and124%in women. The reason for the increasing incidence of ICC is not entirely understood. Several risk factors can predispose an individual to ICC, include primary biliary cirrhosis, primary sclerosing cholangitis, hepatolithiasis, choledochal cyst disease, the use of the radiological contrast agent thorotrast, parasitic biliary infestation (Clonorchis sinensis and Opisthorchis viverrini), Calori’s disease and hepatitis B. Other important risk factors for ICC, hepatitis C and nonalcoholic fatty liver disease (NAFLD), have been increasing in incidence. Recognized by the world that long-term bile duct lesions may be the main reason for the formation of cholangiocarcinoma.Previous studies have shown that the proliferation of cholangiocytes have close link with endocrine system. Endocrine system through a variety of different hormones on the proliferation of cholangiocytes, and the imbalance between proliferation and apoptosis, malignant transformation, formation of cholangiocarcinoma has closely relationship with endocrine system. Related to this, a number of clinical studies have found endocrine system diseases, especially diabetes also participate in the development of the cholangiocarcinoma. Recently, a mata anaysis from Hu et. about whether diabetes increase the risk of choalangiocarcinoma, shows that DM may be the risk factors of cholangiocarcinoma. These studies have shown that the endocrine system disease and bile duct disease and cholangiocarcinoma has closely link. Although diabetes mellitus (DM) has been shown to be risk factors for many cancers, the associations remain inconclusive for ICC.Glucagon like peptide1(GLP-1) is a gut-derived peptide secreted in a nutrient-dependent manner from the small intestine and stimulates glucose-dependent insulin production and secretion via specific receptors expressed on islet b cells. Similar embryonic origin of the pancreas and bile duct system, in recent years, GLP-1on the role of the bile duct system is also gradually be taken seriously. we demonstrated that activation of the GLP-1R in cholangiocytes by its selective agonist exendin-4prevents cholangiocyte apoptosis. Overall, our findings suggest that exendin-4is a molecule that is able to correct the dysregulated balance between cholangiocyte proliferation and apoptosis. Besides being relevant for the understanding of the pathophysiology of chronic cholestasis. While there is no recent study on relationship between GLP-1and intrahepatic cholangiocarcinoma. GLP-1as the intersection of the two areas, has significant meaning of the development of intrahepatic cholangiocarcinoma. Currently, the GLP-1and its analogs Exendin-4research mainly in the field of diabetes treatment, attention on diseases of the biliary system has not yet, in many domestic and international literature precisely the neuroendocrine system and endocrine diseases play an important role of the development of the cholangiocarcinoma, we hope to explore the role of neuroendocrine hormones GLP-1and its receptor expression in human cholangiocarcinoma, how the GLP-1and its analogs Exendin-4work on cholangiocarcinoma cell and intracellular signaling transmission line, while the use of animal models to evaluate the GLP-1analogue Exendin-4in significance in the field of treatment of cholangiocarcinoma extremely.Therefore, in our study63cases of intrahepatic cholangiocarcinoma who were underwent a surgical resection of intrahepatic cholangiocarcinoma, the average survival time of21.6months, the medianthe survival time of18months, among the63cases,13cases have been diagnosis of DM, diabetes is associated with an increased risk for ICC, for the univariate analysis results suggest that, overall prognostic factors including TNM stage, tumor number, tumor size, and portal vein thrombosis, multivariate analysis prompted an independent risk factor affecting the prognosis for TNM staging, as well as the number of tumors. Select hepatocellular carcinoma, normal liver tissue as a control, GLP-1R expression in various tissues, These results suggest that GLP-1R expression in cholangiocarcinoma was significantly higher than that of hepatocellular carcinoma and normal liver tissue, We may also conclude that:GLP-1may be a potential Mark for intrahepatic cholangiocarcinoma, or a treatment of a new target. We found that GLP-1and its analogs Exendin-4tumor cells with a certain degree of inhibition of proliferation, promote apoptosis, further combination chemotherapy drug oxaliplatin with tumor cells, we found that Exendin-4has a sensitizing effect of chemotherapy drugs, it can make tumor formation decreased, and apoptosis increased.With the increase in obesity and type2diabetes, GLP-1in this field of application is also gradually increasing. However, the impact of these drugs on malignant tumors has not been studied thoroughly, however, due to the limited of the sample size and study time, we also need a longer time to come up with more convincing evidence. In conclusion, our study shows that the incretin GLP-1as a strong cAMP inducer, can inhibit the proliferation of intrahepatic cholangiocarcinoma cells. Down regulation of the GLP-1may cause obesity, diabetes patients with a new mechanism of intrahepatic cholangiocarcinoma. |
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