Methylseleninic acid restricts tumor growth in nude mice model of metastatic breast cancer probably via inhibiting angiopoietin-2

BMC Cancer

Research Article

Yin Chen¹  Yidi Zhang²  Runlin Z Ma²  Xiaojing Wu³  Xu Yang³  Si Chen³  Degui Lin³  Zengyang Pei³ 

[1] Department of Pathology, Beijing Sanbo Brain Hospital, 100093, Beijing, China;State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China;The Graduate University of the Chinese Academy of Sciences, 100149, Beijing, China;The Clinical Department, College of Veterinary Medicine, China Agricultural University, 100193, Beijing, China;

关键词: Selenium;    MSeA;    Ang-2;    VEGF;    MDA-MB-231 cells;    Xenograft tumor;   

DOI  :  10.1186/1471-2407-12-192

 received in 2012-01-19, accepted in 2012-05-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAngiopoietin-2 (Ang-2) plays critical roles in vascular morphogenesis and its upregulation is frequently associated with various tumors. Previous studies showed that certain selenium compounds possess anti-tumor effects. However, the underlining mechanism has not been elucidated in detail. Plus, results of research on the anti-tumor effects of selenium compounds remain controversial.MethodsWe investigated levels of Ang-2 and vascular endothelial growth factor (VEGF) on the estrogen-independent bone metastatic mammary cancer (MDA-MB-231) cells in response to treatment by methylseleninic acid (MSeA), and further examined the effects of MSeA oral administration on xenograft mammary tumors of athymic nude mice by RT-PCR, Western, radioimmuno assay, and Immunohistochemistry.ResultsTreatment of MDA-MB-231 cells with MSeA caused significant reduction of Ang-2 mRNA transcripts and secretion of Ang-2 proteins by the cells. Level of VEGF protein was accordingly decreased following the treatment. Compared with the controls, oral administration of MSeA (3 mg/kg/day for 18 days) to the nude mice carrying MDA-MB-231 induced tumors resulted in significant reduction in xenograft tumor volume and weights, significant decrease in microvascular density, and promotion of vascular normalization by increasing pericytes coverage. As expected, level of VEGF was also decreased in MSeA treated tumors.ConclusionsOur results point out that MSeA exerts its anti-tumor effects, at least in part, by inhibiting the Ang-2/Tie2 pathway, probably via inhibiting VEGF.

【 授权许可】

Unknown   
© Wu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.