Park Byung Chul, Thapa Dinesh, Lee Yoon-Seok, Kwak Mi-Kyoung, Lee Eung-Seok, Choi Han Gon, Yong Chul Soon, Kim Jung-Ae
College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan 712-749, South Korea.
Eur J Pharmacol. 2007 Jul 19;567(3):193-7. doi: 10.1016/j.ejphar.2007.04.014. Epub 2007 Apr 21.
Matrix metalloproteinases (MMPs) play important roles in solid tumor invasion and migration. In this study, we showed that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) dose-dependently inhibited HT1080 cell invasion and migration, and decreased MMP-2 and MMP-9 activities. Furthermore, FPP-3 reduced MMP-2 expression at protein and mRNA levels, and suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced expression of MT1-MMP without changing tissue inhibitors of metalloproteinase (TIMP)-2 level. FPP-3 also suppressed TPA-induced increases in MMP-9 protein and mRNA levels, but did not alter TIMP-1 level. Our results suggest that FFP-3 may be a valuable anti-invasive drug candidate for cancer therapy by suppressing MMP-2, MMP-9, and MT1-MMP.
基质金属蛋白酶(MMPs)在实体瘤的侵袭和迁移中发挥着重要作用。在本研究中,我们发现1-呋喃-2-基-3-吡啶-2-基-丙烯酮(FPP-3)呈剂量依赖性地抑制HT1080细胞的侵袭和迁移,并降低MMP-2和MMP-9的活性。此外,FPP-3在蛋白质和mRNA水平上降低了MMP-2的表达,并抑制了12-O-十四酰佛波醇-13-乙酸酯(TPA)增强的MT1-MMP表达,而不改变金属蛋白酶组织抑制剂(TIMP)-2的水平。FPP-3还抑制了TPA诱导的MMP-9蛋白和mRNA水平的增加,但未改变TIMP-1的水平。我们的结果表明,FPP-3可能是一种有价值的抗癌侵袭药物候选物,可通过抑制MMP-2、MMP-9和MT1-MMP发挥作用。