Silibinin Suppresses TNF-α-Induced MMP-9 Expression in Gastric Cancer Cells through Inhibition of the MAPK Pathway

Molecules

Sangmin Kim¹  Min Gew Choi¹  Hye Sook Lee¹  Se Kyung Lee¹  Sung Hoon Kim¹  Wan Wook Kim¹  Sung Mo Hur¹  Jung-Han Kim¹  Jun-Ho Choe¹  Seok Jin Nam¹  Jung-Hyun Yang¹  Sung Kim¹  Jeong Eon Lee¹ 

[1] 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.

关键词: silibinin;    TNF-α;    MMP-9;    gastric cancer;   

DOI  :  10.3390/molecules14114300

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.