Sinomenine influences capacity for invasion and migration in activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, and CD147.
OBJECTIVE
The aim of this study was to investigate the mechanism of the effects of Sinomenine (SIN) on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1). Sinomenine is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum.


METHODS
Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. The invasion and migration ability of cells was tested by in vitro transwell assays. The levels of CD147 and MMPs were evaluated by flow cytometric analysis and zymographic analysis, respectively. The mRNA expression of CD147, MMP-2, and MMP-9 was measured by RT-PCR.


RESULTS
The invasion and migration ability of A-THP-1 cells was significantly inhibited by SIN in a concentration-dependent fashion; at the same time, the levels of CD147, MMP-2, and MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 mmol/L and 1.00 mmol/L (P<0.01).


CONCLUSIONS
A possible mechanism of the inhibitory effect of SIN on cell invasion and migration ability is repression of the expression of MMP-2 and MMP-9, which strongly correlates with the inhibition of CD147 activity.
Ou
Yang-qiong
YQ
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Chen
Li-hua
LH
Li
Xue-jun
XJ
Lin
Zhi-bin
ZB
Li
Wei-dong
WD
D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D051926:Basigin / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009019:Morphinans / Q000494:pharmacology* / Q000627:therapeutic use
C497886:BSG protein, human; D007166:Immunosuppressive Agents; D061965:Matrix Metalloproteinase Inhibitors; D009019:Morphinans; D051926:Basigin; C009271:sinomenine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9