Department of Rehabilitation Medicine, Eulji University Hospital, Daejeon 302-799, Korea.
Mol Cells. 2010 Feb 28;29(2):209-15. doi: 10.1007/s10059-010-0028-9.
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of bee venom (BV) and its major peptides, melittin and apamin, on PMA-induced invasion induced by MMP-9 expression in Caki-1 renal cancer cells. BV and melittin, but not apamin, significantly suppressed PMA-induced invasion by inhibiting MMP-9 expression in Caki-1 cells. Furthermore, as evidenced by MMP-9 promoter assays, melittin inhibited MMP-9 gene expression by blocking the PMA-stimulated activations of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB). In addition, melittin suppressed the PMA-induced phosphorylations of ERK and JNK mitogen-activated protein kinases, upstream factors involved in Ap-1 and NF-kappaB. These results suggest that the suppression of MMP-9 expression contributes to the anti-tumor properties of melittin.
基质金属蛋白酶-9（MMP-9）在癌细胞的侵袭和转移中起着重要作用。在这项研究中，我们研究了蜂毒（BV）及其主要肽，蜂毒素和蜂毒肽，对 PMA 诱导的 MMP-9 表达诱导的 Caki-1 肾癌细胞侵袭的抑制作用。BV 和蜂毒素，但不是蜂毒肽，显著抑制 PMA 诱导的侵袭通过抑制 MMP-9 在 Caki-1 细胞中的表达。此外，正如 MMP-9 启动子试验所证明的那样，蜂毒素通过阻断 PMA 刺激的激活蛋白-1（AP-1）和核因子-kappa B（NF-kappaB）的激活来抑制 MMP-9 基因表达。此外，蜂毒素抑制 PMA 诱导的 ERK 和 JNK 丝裂原激活蛋白激酶的磷酸化，这是涉及 Ap-1 和 NF-kappaB 的上游因子。这些结果表明，抑制 MMP-9 的表达有助于蜂毒素的抗肿瘤特性。
