文档介绍：β肾上腺素能受体与胰腺癌关系的研究进展
(作者:___________单位: ___________邮编: ___________)
【摘要】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kras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。
【关键词】β肾上腺素能受体;胰腺癌;危险因素;受体通路
ABSTRACT: βadrenoceptor, whose subtypes β1 and β2adrenoceptor are expressed on panreatic cancer cells, is closely related to the occurrence and development of pancreatic cancer. βadrenoceptor agonists epirenamine, isopropylarterenol and the o
specific nitrosamine 4(methylnitrosamino)1(3pyridyl)1butanone (NNK) induce pancreatic cancer proliferation. Research on the molecular mechanism is as follows: Activating βreceptor 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. βadrenoceptor can make the epidermal growth factor (EGFR) pathway transactivated, and the EGFR and βadrenergic 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 βadrenoceptor in cardiovascular diseases might be used for the prevention and treatment of pancreatic cancer.
KEY WORDS: βadrenoceptor; pancreatic cancer; risk factor; receptor pathway
胰腺癌是一种较常见的恶性肿瘤,目前尚无有效的筛查或早期诊断方法,确诊时往往已有转移,手术切除率低、预后差,死亡率几乎接近其发病率。进行胰腺癌的发病机理的研究对胰腺癌的预防、诊断和治疗非常重要[1]。
1 胰腺癌的流行病学
2008年美国胰腺癌新发病例
37680例,其中男性18770例,女性18910例,占全部恶性肿瘤新发病例的3%;同年胰腺癌死亡例数为34290,与发病例数接近,男性17500例,女性17690例,占全部恶性肿瘤死亡的6%,位居恶性肿瘤死亡的第4位[2]。胰腺癌的发病水平与社会经济状况有一定关系。据估计,,。胰腺癌的发病率和死亡率有明显的地理差异,高发国家或地区的发病率可以是低发区的5~7倍。在发达国