Kim So-Young, Lee Eun-Jung, Woo Moon-Sook, Jung Ji-Sun, Hyun Jin-Won, Min Sung-Won, Kim Dong-Hyun, Kim Hee-Sun
Department of Neuroscience and Medical Research Institute, College of Medicine, Ewha Womans University, Mok-6-dong 911-1, Yangchun-Ku, Seoul 158-710, Republic of Korea.
Biochem Biophys Res Commun. 2008 Feb 8;366(2):493-9. doi: 10.1016/j.bbrc.2007.11.178. Epub 2007 Dec 10.
Matrix metalloproteinase-9 (MMP-9) plays an important role in mediating the invasion and angiogenic process of malignant gliomas. This study was undertaken to determine if an isoflavone metabolite, irisolidone, inhibits MMP-9 expression in human astroglioma cells. Irisolidone was found to inhibit the secretion and protein expression of MMP-9 induced by PMA in U87 MG glioma cells, accompanied by the inhibition of MMP-9 mRNA expression and promoter activity. Further mechanistic studies revealed that irisolidone inhibits the binding of NF-kappaB and AP-1 to the MMP-9 promoter and suppresses the PMA-induced phosphorylation of ERK and JNK, which are upstream signaling molecules in MMP-9 expression. The Matrigel-invasion assay showed that irisolidone suppresses the in vitro invasiveness of glioma cells. Therefore, the strong inhibition of MMP-9 expression by irisolidone might be a potential therapeutic modality for controlling the growth and invasiveness of gliomas.
基质金属蛋白酶-9（MMP-9）在介导恶性胶质瘤的侵袭和血管生成过程中起重要作用。本研究旨在确定一种异黄酮代谢产物鸢尾酮是否能抑制人星形胶质瘤细胞中MMP-9的表达。研究发现鸢尾酮可抑制U87 MG胶质瘤细胞中由佛波酯（PMA）诱导的MMP-9分泌和蛋白表达，同时抑制MMP-9 mRNA表达和启动子活性。进一步的机制研究表明，鸢尾酮可抑制核因子κB（NF-κB）和激活蛋白-1（AP-1）与MMP-9启动子的结合，并抑制PMA诱导的细胞外信号调节激酶（ERK）和应激活化蛋白激酶（JNK）的磷酸化，而ERK和JNK是MMP-9表达的上游信号分子。基质胶侵袭试验表明鸢尾酮可抑制胶质瘤细胞的体外侵袭能力。因此，鸢尾酮对MMP-9表达的强烈抑制作用可能是控制胶质瘤生长和侵袭的一种潜在治疗方式。
