文献类型：期刊文献

英文题名：AMD3100 inhibits brain-specific metastasis in lung cancer via suppressing the SDF-1/CXCR4 axis and protecting blood-brain barrier

作者：Li, Hongru[1,2];Chen, Yusheng[1,2];Xu, Nengluan[1,2];Yu, Meie[1];Tu, Xunwei[1];Chen, Zhengwei[1];Lin, Ming[1];Xie, Baosong[1];Fu, Jianjun[3];Han, Lili[4]

机构：[1]Fujian Med Univ, Fujian Prov Hosp, Dept Resp Med & Crit Care Med, Fujian Prov Coll, 134 East St, Fuzhou 350001, Fujian, Peoples R China;[2]Fujian Inst Four Resp Dis, Fuzhou 350001, Fujian, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[4]Fujian Key Lab Cardiovasc Dis, Fuzhou 350001, Fujian, Peoples R China

年份：2017

卷号：9

期号：12

起止页码：5259

外文期刊名：AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000419213500006)】；

基金：This work was supported by National Health and Family Planning Commission Science Research Fund-the Joint tackling key problem plan of department of sanitation and education of Fujian province, China (WKJ-FJ-17); Natural Science Foundation of Fujian Province, China (2015J01376), and Excellent Young Physician Project of Fujian Provincial Hospital, China (2014YNQN03).

语种：英文

外文关键词：Brain metastasis; SDF-1; CXCR4; AMD3100; lung cancer

摘要：Lung cancer represents the foremost cause of cancer-related mortality in both men and women throughout the world. Metastasis to the brain constitutes a major problem in the management of patients with lung cancer. However, the mechanism of brain-specific metastasis in lung cancer has not been fully elucidated. Chemokines and their receptors have emerged as attractive targets regulating the cancer metastasis. It has been discovered that the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis plays a critical role in determining the metastatic destination of tumor cells. In this study, strong expression of SDF-1 was observed in highly metastatic brain tissues, and CXCR4 overexpressed in PC-9 lung cancer cells and tumor foci. Therefore, we chose to block SDF-1/CXCR4 axis with AMD3100, which led to the increased tight junction protein level, less damage, and decreased permeability of blood-brain barrier (BBB). Consequently, the process of lung cancer metastasis to the brain was significantly slowed down. These findings were further validated by in vivo experiments, which showed that AMD3100 can effectively inhibit lung cancer brain metastasis and extend the survival of nude mice model, suggesting that it is a potential drug candidate for inhibiting the lung cancer metastasis to brain. These findings provided valuable information for designing new therapeutic strategies for the treatment of lung cancer brain metastasis.