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Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway
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; in revised form: 10 October 2009 / Accepted: 19 October 2009 / Published: 26 October 2009
Abstract: 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
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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.
Kim S, Choi MG, Lee HS, Lee SK, Kim SH, Kim WW, Hur SM, Kim J-H, Choe J-H, Nam SJ, Yang J-H, Kim S, Lee JE, Kim JS. Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway. Molecules. 2009; 14(11):4300-4311.
Kim, Sangmin; Choi, Min G.; Lee, Hye S.; Lee, Se K.; Kim, Sung H.; Kim, Wan W.; Hur, Sung M.; Kim, Jung-Han; Choe, Jun-Ho; Nam, Seok J.; Yang, Jung-Hyun; Kim, Sung; Lee, Jeong E.; Kim, Jee S. 2009. "Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway." Molecules 14, no. 11: 4300-4311.