Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway.
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.
Kim
Sangmin
S
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Choi
Min Gew
MG
Lee
Hye Sook
HS
Lee
Se Kyung
SK
Kim
Sung Hoon
SH
Kim
Wan Wook
WW
Hur
Sung Mo
SM
Kim
Jung-Han
JH
Choe
Jun-Ho
JH
Nam
Seok Jin
SJ
Yang
Jung-Hyun
JH
Kim
Sung
S
Lee
Jeong Eon
JE
Kim
Jee Soo
JS
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*
D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; D020780:Matrix Metalloproteinase 9