| 摘要: | Background/Purpose: Betel quid extract (BQE) has been demonstrated to induce matrix metalloproteinase
(MMP)-2 expression. This study aimed to establish the possible mechanism involved in this event.
Methods: Western blotting, reverse-transcription polymerase chain reaction, and gelatin zymography were
used to study the expression level of MMP-2. LY294002, PD98059, U0126, N-acetyl-L-cysteine, SB203580,
SP600125, and Bay 11-7082 were used to pretreat OECM-1 cells before BQE treatment and MMP-2 detection.
Results: OECM-1 cells were subjected to short-term (10 minutes) or long-term (24 hours) BQE treatment
(designated as SBT and LBT, respectively), and we found that both treatments increased MMP-2 protein and extracellular
signal-regulated kinase (ERK) phosphorylation levels in a concentration- and time-dependent manner.
LBT also increased MMP-2 mRNA level. LBT-induced MMP-2 secretion was not inhibited by PD98059 (up
to 50 μM) when ERK was effectively blocked, but was attenuated by LY294002 (0–10 μM) in a concentrationdependent
manner. This LBT effect was inhibited strongly by SB203580 (10 μM), SP600125 (10 μM), and
Bay 11-7082 (10 μM) and mildly by N-acetyl-L-cysteine (5 mM), but not by U0126 (10 μM).
Conclusion: Both SBT and LBT upregulate MMP-2 expression, and LBT-induced MMP-2 expression might be
mediated by phosphoinositide 3-kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase,
and nuclear factor-κB, and to a lesser extent, by reactive oxygen species, rather than by ERK. |
