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- Title
Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway.
- Authors
Sangmin Kim; Min Gew Choi; Hye Sook Lee; Se Kyung Lee; Sung Hoon Kim; Wan Wook Kim; Sung Mo Hur; Jung-Han Kim; Jun-Ho Choe; Seok Jin Nam; Jung-Hyun Yang; Sung Kim; Jeong Eon Lee; Jee Soo Kim
- 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.
- Subjects
TUMOR necrosis factors; CYTOKINES; HELICOBACTER pylori; GASTRIC acid; CANCER cells; MESSENGER RNA; APOPTOSIS; CELL cycle; WESTERN immunoblotting
- Publication
Molecules, 2009, Vol 14, Issue 11, p4300
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules14114300