RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation
Leung,Hoi-Wing; Zhao,Si-Meng; Yue,Grace Gar-Lee; Lee,Julia Kin-Ming; Fung,Kwok-Pui; Leung,Ping-Chung; Tan,Ning-Hua; Lau,Clara Bik-San
2015-11-23
Source PublicationSCIENTIFIC REPORTS
Volume5
AbstractCancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer.
DOI10.1038/srep16985
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000365239400003
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/25252
Collection植物化学与西部植物资源持续利用国家重点实验室
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Leung,Hoi-Wing,Zhao,Si-Meng,Yue,Grace Gar-Lee,et al. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation[J]. SCIENTIFIC REPORTS,2015,5.
APA Leung,Hoi-Wing.,Zhao,Si-Meng.,Yue,Grace Gar-Lee.,Lee,Julia Kin-Ming.,Fung,Kwok-Pui.,...&Lau,Clara Bik-San.(2015).RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation.SCIENTIFIC REPORTS,5.
MLA Leung,Hoi-Wing,et al."RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation".SCIENTIFIC REPORTS 5(2015).
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