水飞蓟宾通过抑制 MAPK 通路抑制 TNF-α诱导的胃癌细胞 MMP-9 的表达。
Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway.
机构信息
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
出版信息
Molecules. 2009 Oct 26;14(11):4300-11. doi: 10.3390/molecules14114300.
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.
肿瘤坏死因子 (TNF)-α 是幽门螺杆菌中高度表达的促炎细胞因子之一，可抑制胃酸分泌。在本研究中，我们确定了水飞蓟素对 TNF-α 诱导的胃癌细胞系中 MMP-9 表达的影响。TNF-α 在 SNU216 和 SNU668 胃癌细胞中呈剂量依赖性增加 MMP-9 mRNA 和蛋白表达。另一方面，水飞蓟素呈剂量依赖性抑制 TNF-α 诱导的 MMP-9 表达。为了验证水飞蓟素对 TNF-α 诱导的 MMP-9 表达的调节机制，在 TNF-α 之前用水飞蓟素预处理胃癌细胞系。MEK1/2 特异性抑制剂 UO126 抑制 TNF-α 诱导的 MMP-9 表达。最后，我们研究了腺病毒组成型激活 (CA)-MEK 和 CA-Akt 对 MMP-9 表达的影响。过表达 CA-MEK 可显著增加 MMP-9 的表达，但过表达 CA-Akt 则不然。总之，我们认为水飞蓟素通过抑制胃癌细胞中的 MEK/ERK 通路下调 TNF-α 诱导的 MMP-9 表达。
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