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Molecules 2009, 14(11), 4300-4311; doi:10.3390/molecules14114300

Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway

, , , , , , , , , , , , *  and *
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul, Korea These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 7 September 2009 / Revised: 10 October 2009 / Accepted: 19 October 2009 / Published: 26 October 2009
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Tumor necrosis factor (TNF)-α is one of the pro-inflammatory cytokines highly expressed in Helicobacter pylori that inhibits gastric acid secretion. In this study we determined the effect of silibinin on TNF-α-induced MMP-9 expression in gastric cancer cell lines. MMP-9 mRNA and protein expression was dose-dependently increased by TNF-α in SNU216 and SNU668 gastric cancer cells. On the other hand, TNF-α-induced MMP-9 expression was dose-dependently suppressed by silibinin. To verify the regulatory mechanism of silibinin on TNF-α-induced MMP-9 expression, the gastric cancer cell lines were pretreated with silibinin prior to TNF-α. TNF-α-induced MMP-9 expression was inhibited by the MEK1/2 specific inhibitor, UO126. Finally, we investigated the effect of adenoviral constitutively active (CA)-MEK and CA-Akt on MMP-9 expression. The expression of MMP-9 was significantly increased by CA-MEK overexpression, but not by CA-Akt overexpression. Taken together, we suggest that silibinin down-regulates TNF-α- induced MMP-9 expression through inhibition of the MEK/ERK pathway in gastric cancer cells.
Keywords: silibinin; TNF-α; MMP-9; gastric cancer silibinin; TNF-α; MMP-9; gastric cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kim, S.; Choi, M.G.; Lee, H.S.; Lee, S.K.; Kim, S.H.; Kim, W.W.; Hur, S.M.; Kim, J.-H.; Choe, J.-H.; Nam, S.J.; Yang, J.-H.; Kim, S.; Lee, J.E.; Kim, J.S. Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway. Molecules 2009, 14, 4300-4311.

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