去甲肾上腺素在抑郁状态下提高乳腺癌的恶性程度  

Norepinephrine increases risk of breast cancer in depressed women

作　　者：欧阳雪岩 朱朕 杨超 王丽 丁罡[1,4] 姜峰 OUYANG Xue-yan;ZHU Zhen;YANG Chao;WANG Li;DING Gang;JIANG Feng(School of Medicine,Shanghai Jiao Tong University,Shanghai 200025,China;College of Life Sciences,Shanghai University,Shanghai 200444,China;Institute of Cancer-pain Transformation,Chongming Branch,Xinhua Hospital,Shanghai Jiao TongUniversity,Shanghai 202150,China;Shanghai International Medical Center,Shanghai 201318,China)

机构地区：[1]上海交通大学医学院,上海200025 [2]上海大学生命科学学院,上海200444 [3]上海交通大学医学院附属新华医院崇明分院癌痛转化研究所,上海202150 [4]上海国际医学中心,上海201318

出　　处：《中国药理学通报》2019年第10期1381-1387,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81572859);上海市卫生和计划生育委员会面上项目(No 201740027)

摘　　要：目的探究抑郁对肿瘤的影响及其可能的分子机制。方法构建慢性轻度不可预见性应激模型(CUMS),行为学检测后接种肿瘤,检测血清去甲肾上腺素以及肿瘤体积组间差异;给药刺激乳腺癌细胞并检测侵袭、迁移、增殖及细胞周期分布;免疫印迹及免疫荧光检测细胞表面受体及胞内信号通路。结果抑郁上调去甲肾上腺素水平,使p38MAPK的磷酸化程度增强,并导致乳腺癌细胞恶性程度增加。结论抑郁通过去甲肾上腺素激活肾上腺素β受体,促进p38MAPK信号通路磷酸化,从而增加乳腺癌的恶性程度。Aim To explore the effects of depression on tumors,as well as its molecular mechanisms.Methods The chronic unpredictable mild stress model (CUMS) was constructed.Tumor was inoculated after behavioral test,and the differences in serum norepinephrine and tumor volume between groups were detected.Breast cancer cells were stimulated by administration and invasion,migration,proliferation and cell cycle distribution were detected.Western blot and immunofluorescence were utilized to detect cell surface receptors and intracellular signaling pathways.Results Depression up-regulated the level of norepinephrine (NE) and increased the phosphorylation of p38 MAPK,resulting in increased malignancy of breast cancer cells.Conclusions Depression may increase the malignancy of breast cancer through norepinephrine-induced p38 MAPK signaling pathway,thus increasing the malignant degree of breast cancer.

关 键 词：抑郁 乳腺癌 慢性轻度不可预见性应激模型 去甲肾上腺素 P38MAPK 肾上腺素β受体 

分 类 号：R-332[医药卫生] R329.24