title: Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway.
abstract: Tumor necrosis factor (TNF)-alpha 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-alpha-induced MMP-9 expression in gastric cancer cell lines. MMP-9 mRNA and protein expression was dose-dependently increased by TNF-alpha in SNU216 and SNU668 gastric cancer cells. On the other hand, TNF-alpha-induced MMP-9 expression was dose-dependently suppressed by silibinin. To verify the regulatory mechanism of silibinin on TNF-alpha-induced MMP-9 expression, the gastric cancer cell lines were pretreated with silibinin prior to TNF-alpha. TNF-alpha-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-alpha- induced MMP-9 expression through inhibition of the MEK/ERK pathway in gastric cancer cells.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.forename: Min Gew
authors.initials: MG
authors.lastname: Choi
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Lee
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Wan Wook
authors.initials: WW
authors.lastname: Kim
authors.forename: Sung Mo
authors.initials: SM
authors.lastname: Hur
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choe
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Yang
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Jee Soo
authors.initials: JS
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; D020780:Matrix Metalloproteinase 9