In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 19, No. 2 ( 2015-02), p. 383-395
Abstract:
Cell migration and invasion are key processes in the metastasis of cancer, and suppression of these steps is a promising strategy for cancer therapeutics. The aim of this study was to explore small molecules for treating colorectal cancer ( CRC ) and to investigate their anti‐metastatic mechanisms. In this study, six CRC cell lines were used. We showed that YH ‐306 significantly inhibited the migration and invasion of CRC cells in a dose‐dependent manner. In addition, YH ‐306 inhibited cell adhesion and protrusion formation of HCT 116 and HT ‐29 CRC cells. Moreover, YH ‐306 potently suppressed uninhibited proliferation in all six CRC cell lines tested and induced cell apoptosis in four cell lines. Furthermore, YH ‐306 inhibited CRC colonization in vitro and suppressed CRC growth in a xenograft mouse model, as well as hepatic/pulmonary metastasis in vivo . YH ‐306 suppressed the activation of focal adhesion kinase ( FAK ), c‐Src, paxillin, and phosphatidylinositol 3‐kinases ( PI 3K), Rac1 and the expression of matrix metalloproteases ( MMP ) 2 and MMP 9. Meanwhile, YH ‐306 also inhibited actin‐related protein (Arp2/3) complex‐mediated actin polymerization. Taken together, YH ‐306 is a candidate drug in preventing growth and metastasis of CRC by modulating FAK signalling pathway.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2015.19.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2076114-4
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