β肾上腺素能受体与胰腺癌关系的研究进展

Advance of study on relationship between β-adrenoceptor and pancreatic cancer

β肾上腺素能受体与胰腺癌的发生发展有着密切的关系,胰腺癌细胞表面表达β1和β2受体。β受体激动剂肾上腺素、异丙肾上腺素和亚硝基4-(甲基亚硝基)-1-(3-吡啶基)-1-丁酮(NNK)可以刺激胰腺癌细胞增殖。关于其分子机制的研究有:①激活β受体可以刺激花生四烯酸(AA)的代谢通路,导致AA代谢产物的增加并激活转录因子;②NNK诱导k-ras基因的突变导致细胞分裂素活化蛋白激酶通路的激活;③通过β受体的激活可以转活表皮生长因子受体通路。胰腺癌的危险因素在心血管系统疾病中也存在,如吸烟和精神因素。目前用于治疗心血管系统疾病的药物β受体阻滞剂可能可以用于胰腺癌的预防和治疗。

β-adrenoceptor,whose subtypes β1-and β2-adrenoceptor are expressed on panreatic cancer cells,is closely related to the occurrence and development of pancreatic cancer.β-adrenoceptor agonists epirenamine,isopropylarterenol and the tobacco-specific nitrosamine 4-（methylnitrosamino）-1-（3-pyridyl）-1-butanone（NNK） induce pancreatic cancer proliferation.Research on the molecular mechanism is as follows： Activating β-receptor can stimulate protein kinase A（PKA）/arachidonic acid（AA） pathway in pancreatic cancer cells.NNK also stimulates mutation of Ras and the activation of Src tyrosine kinase and Ras,followed by activation of mitogen activated protein kinase（MAPK） pathway.β-adrenoceptor can make the epidermal growth factor（EGFR） pathway transactivated,and the EGFR and β-adrenergic signalling pathways might synergize to activate Src and Ras.Increased evidence suggests that patients with pancreatic adenocarcinoma share many risk factors,such as smoking and chronic depression,with cardiovascular disease patients.Drugs to block β-adrenoceptor in cardiovascular diseases might be used for the prevention and treatment of pancreatic cancer.