Open AccessA novel synthetic small molecule YH ‐306 suppresses colorectal tumour growth and metastasis via FAK pathway
Author(s) -
Dai Fujun,
Chen Yihua,
Huang Li,
Wang Jinhua,
Zhang Tao,
Li Jingjie,
Tong Weiguang,
Liu Mingyao,
Yi Zhengfang
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12450
Subject(s) - metastasis , chemistry , colorectal cancer , molecule , cancer research , microbiology and biotechnology , biology , cancer , genetics , organic chemistry
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.