Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway 英文参考文献.docVIP

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Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway 英文参考文献.doc

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Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway 英文参考文献

Molecules 2009, 14, 4300-4311; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway 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 * and Jee Soo Kim * 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; E-Mails: paojlus@ (J-E.L.), js0507.kim@ (J-S.K.); Tel.: +82-2-3410-0260 (J-E.L.), +82-2-3410-0253 (J-S.K.); Fax: +82-2-3410-6982 (J-E.L.), +82-2-3410-6982 (J-S.K.). 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 togethe