Coptisine suppresses tumor growth and progression by down-regulating MFG-E8 in colorectal cancer

Abstract

Treating colorectal cancer (CRC) continues to be a clinical challenge. Coptisine, an alkaloid derived from <i>Coptis chinensis</i> Franch. shows toxic effects on CRC cells, but its underlying mechanism remains elusive. MFG-E8 is involved in tumor growth and progression. Herein, we evaluated the effects of coptisine on MFG-E8 in CRC, and explored the mechanism. The expression of MFG-E8 in CRC and adjacent normal colon tissue samples from patients was detected. The effects of coptisine on CRC cells HCT116 <i>in vitro</i> were evaluated by CCK-8, adhesion and transwell assays. A xenograft tumor model was used to assess the effects of coptisine <i>in vivo</i>. The morphology of CRC tissue was observed by HE staining. Cell signaling was tested using western blotting and immunohistochemical assay. The expression of MFG-E8 in human CRC tissue samples significantly increased compared with that of adjacent normal ones. Coptisine significantly reduced the expressions of MFG-E8 in HCT116 cells and tumor-bearing mice. Moreover, coptisine suppressed the growth, adhesion and metastasis of CRC cells. Coptisine also suppressed the expression of MMP-2 and MMP-9 <i>via</i> the PI3K/AKT signaling pathway. Furthermore, it inhibited epithelial-mesenchymal transition <i>in vivo</i> and <i>in vitro</i>. Coptisine inhibited CRC growth and progression by down-regulating MFG-E8, and is a potential candidate for treatment.