Xia M, Ji N-N, Duan M-L, Tong J-H, Xu J-G, Zhang Y-M, Wang S-H
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Eur Rev Med Pharmacol Sci. 2016 Aug;20(16):3500-6.
Breast cancer is one of the most aggressive and pervasive cancers identified in females. Dexmedetomidine (Dex) is an efficient anesthetic used in surgery. Our study aimed to explore the role of Dex in the malignancy of breast cancer cells in vitro and in vivo. Further, we investigate the molecular mechanism involved in the function of Dex on breast cancer cells.
The methyl thiazolyl tetrazolium (MTT) assay was applied to detect cell proliferation. The migration and invasion capacity of MDA-MB-231 cells was tested by wound healing assay and transwell assay. Western blot analysis was performed to quantify the protein expression levels of α2-adrenoceptor and ERK.
The proliferation, migration and invasion ability of MDA-MB-231 cells was gradually increased after treatment of Dex in a dose-dependent manner in vitro. In addition, Dex could significantly elevate the volume and weight of xenotransplant tumor in vivo. Furthermore, Dex up-regulated the protein level of a2-adrenoceptor and consistently enhanced the phosphorylation of ERK without changing the total level of it. Similarity, over-expression of a2-adrenoceptor via its agonist Clonidine could mimic the function of Dex on breast cancer.
These data suggest that Dex could promote the proliferation, migration and invasion of breast cancer cells through the activation of α2B-adrenoceptor /ERK signaling.
乳腺癌是女性中最具侵袭性和普遍性的癌症之一。右美托咪定（Dex）是一种用于手术的有效麻醉剂。我们的研究旨在探讨Dex在体外和体内对乳腺癌细胞恶性程度的作用。此外，我们还研究了Dex对乳腺癌细胞功能的分子机制。
采用甲基噻唑基四氮唑蓝（MTT）法检测细胞增殖。通过伤口愈合试验和Transwell试验检测MDA-MB-231细胞的迁移和侵袭能力。进行蛋白质印迹分析以定量α2-肾上腺素能受体和ERK的蛋白质表达水平。
体外给予Dex处理后，MDA-MB-231细胞的增殖、迁移和侵袭能力呈剂量依赖性逐渐增加。此外，Dex可显著增加体内异种移植肿瘤的体积和重量。此外，Dex上调了α2-肾上腺素能受体的蛋白水平，并持续增强ERK的磷酸化水平，而不改变其总水平。同样，通过其激动剂可乐定过表达α2-肾上腺素能受体可模拟Dex对乳腺癌的作用。
这些数据表明，Dex可通过激活α2B-肾上腺素能受体/ERK信号促进乳腺癌细胞的增殖、迁移和侵袭。
