Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, ROC.
Anticancer Res. 2010 Jun;30(6):2135-43.
Cell motility involves metastasis suppressors and other regulators that play an important role in tumor invasion and metastasis. Phenethyl isothiocyanate (PEITC), found in dietary cruciferous vegetables, has been found to exhibit antitumor properties and therefore is of special interest for the development of chemopreventive and chemotherapeutic agent for human cancers. Here, we report that in addition to its function as an anticancer agent, and PEITC can inhibit migration and invasion through the extracellular signal-regulated kinases 1/2 (ERK1/2), protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) signaling pathways in human gastric cells. The results from wound healing and Boyden chamber assays (migration and invasion) assay indicated that PEITC exhibited an inhibitory effect on the migration and invasion of AGS cells. Results from Western blotting examination demonstrated that PEITC exerted an inhibitory effect on the ERK1/2, mitogen-activated protein kinase kinase 7 (MKK7), MAP kinase kinase kinase 3 (MEKK3), son of sevenless 1 (SOS1), PKC, Ras homolog gene family, member A (Rho A) and urokinase-type plasminogen activator (uPA), causing the inhibition of matrix metallopeptidase-2 (MMP-2) and -9 then followed by the inhibition of invasion and migration of GAS cells in vitro. PEITC also inhibited Ras, growth factor receptor-bound protein 2 (GRB2), vascular endothelial growth factor (VEGF), focal adhesion kinase (FAK), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), causing inhibition of cell proliferation of AGS cells. Results from real-time PCR showed that PEITC inhibited the gene expressions of MMP-2, -7 and -9, FAK and RhoA after PEITC treatment for 24 and 48 h of AGS cells. Taken together, these findings may provide insight into a new mechanisms and functions of PEITC in migration and invasion of human gastric cancer AGS cells. Our data imply that molecular targeting of PKC leading to the inhibition of MMP-2 and -9 might be a useful strategy for the inhibition of migration and invasion of human gastric cancer.
细胞运动涉及转移抑制因子和其他调节剂，它们在肿瘤侵袭和转移中发挥重要作用。存在于十字花科蔬菜中的苯乙基异硫氰酸酯（PEITC）已被发现具有抗肿瘤特性，因此对于开发用于人类癌症的化学预防和化学治疗剂具有特殊意义。在这里，我们报告说，除了作为抗癌剂的功能外，PEITC 还可以通过细胞外信号调节激酶 1/2（ERK1/2）、蛋白激酶 C（PKC）和核因子-κB（NF-κB）信号通路抑制人胃细胞的迁移和侵袭。伤口愈合和 Boyden 室测定（迁移和侵袭）的结果表明，PEITC 对 AGS 细胞的迁移和侵袭具有抑制作用。Western blot 检测结果表明，PEITC 对 ERK1/2、丝裂原激活蛋白激酶激酶 7（MKK7）、MAP 激酶激酶激酶 3（MEKK3）、SOS1、PKC、Ras 同源基因家族成员 A（Rho A）和尿激酶型纤溶酶原激活物（uPA）发挥抑制作用，从而抑制基质金属蛋白酶-2（MMP-2）和 -9，随后抑制体外 GAS 细胞的侵袭和迁移。PEITC 还抑制 Ras、生长因子受体结合蛋白 2（GRB2）、血管内皮生长因子（VEGF）、粘着斑激酶（FAK）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2），从而抑制 AGS 细胞的细胞增殖。实时 PCR 结果表明，PEITC 抑制了 MMP-2、-7 和 -9、FAK 和 RhoA 的基因表达，PEITC 处理 AGS 细胞 24 和 48 小时后。综上所述，这些发现可能为 PEITC 抑制人胃癌 AGS 细胞迁移和侵袭的新机制和功能提供了新的认识。我们的数据表明，PKC 的分子靶向导致 MMP-2 和 -9 的抑制可能是抑制人类胃癌迁移和侵袭的一种有用策略。
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