Clinical Significance Of α₁-Adrenergic Receptor's Expression And Its Effect On Cholangiocar Cinomas's Proliferation

Purpose: Recently, increasing evidences suggested that norepinephrine(NE) and its receptors were involved in cancer invasion and metastasis,meanwhile,many studys found the abnormal distribution of adrenergic receptors in a veriaty of tumors such as oophoroma and liver cancer. In our previous study, the neural pro-tropic of cholangiocarcinoma (CC) was revealed. And some other researches suggest thatα1-adrenergic receptor might play an important role in proliferation and apoptosis of various tumors such as prostate cancer and colon cancer. So we investigated the correlation between the expression ofα1-adrenergic receptor and its biologic behavior in cholangiocarcinomas. As previous studies have proved that NE could promote the proliferation of hepatoma carcinoma cell by stimulating theα1-adrenergic receptor, so we observed the effect of NE in the proliferation process of bile duct carcinoma cell line (QBC939), which could probobaly imply the participation ofα1-adrenergic receptor in the proliferation and metastasis of cholangiocarcinoma.Experimental Design: In the first part of the experiment,α1-adrenergic receptor was detectived with the immunohistochemical staining in the samples of cholangiocarcinoma, their correlation and clinicopathological significance was accessed by statistical methods . In the second part of the experiment, The cells of QBC939 cell line were cultured and exposed to NE with or without the presence ofα1-adrenergic receptor's antagonists. Alamar-blue assay was employed to determine the proliferation of the cell line and then the results were analyzed.Results:1. The percentage of the positive and high positive expression rate ofα1-adrenergic receptor in 36 cases of cholangiocarcinoma were 86.1 % and 50 % , respectively. There were significant differences ofα1-adrenergic receptor ( P < 0.05) between the different lacations of cholangiocarcinoma. The metastatic rate of tumor stained positively forα1-adrenergic receptor was higher than in that with negative staining ( P < 0.05).2. NE could increase the proliferative response in QBC939, and the effect could be reduced by the antagonists ofα1-adrenergic receptor such as phentolamine and prazosin. Besides, the antagonists alone wouldn't restrain the proliferation of QBC939.Conclusion:1. Compared with the normal bile duct, the CC cell had a high expression ofα1-adrenergic receptor, and its strong positive expression was observed mostly in the cases which had lymph node metastasis or distant metastasis, suggestingα1-adrenergic receptor participates the process of cholangiocarcinoma's metastasis.2. Take advantage of the present experimental conditions,β2-adrenergic receptor had a low expression on both normal bile duct and CC.3. From the study of NE and QBC939, NE was found the ability of promoting the proliferation of QBC939. Furthermore,α1-adrenergic receptor, which was abnormal distributed in cholangiocarcinoma, may play a critical role in the process.