蜂毒通过 JNK/p38 和 NF-κB 依赖的机制抑制 PMA 介导的 MMP-9 基因激活。
Bee venom suppresses PMA-mediated MMP-9 gene activation via JNK/p38 and NF-kappaB-dependent mechanisms.
机构信息
Research Institute of Biomedical Engineering, Department of Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
出版信息
J Ethnopharmacol. 2010 Feb 17;127(3):662-8. doi: 10.1016/j.jep.2009.12.007. Epub 2009 Dec 5.
ETHNOPHARMACOLOGICAL RELEVANCE
Bee venom has been used for the treatment of inflammatory diseases such as rheumatoid arthritis and for the relief of pain in traditional oriental medicine.
AIM OF THE STUDY
The purpose of this study is to elucidate the effects of bee venom on MMP-9 expression and determine possible mechanisms by which bee venom relieves or prevents the expression of MMP-9 during invasion and metastasis of breast cancer cells. We examined the expression and activity of MMP-9 and possible signaling pathway affected in PMA-induced MCF-7 cells.
MATERIAL AND METHODS
Bee venom was obtained from the National Institute of Agricultural Science and Technology of Korea. Matrigel invasion assay, wound-healing assay, zymography assay, western blot assay, electrophoretic mobility shift assay and luciferase gene assay were used for assessment.
RESULTS
Bee venom inhibited cell invasion and migration, and also suppressed MMP-9 activity and expression, processes related to tumor invasion and metastasis, in PMA-induced MCF-7 cells. Bee venom specifically suppressed the phosphorylation of p38/JNK and at the same time, suppressed the protein expression, DNA binding and promoter activity of NF-kappaB. The levels of phosphorylated ERK1/2 and c-Jun did not change. We also investigated MMP-9 inhibition by melittin, apamin and PLA(2), representative single component of bee venom. We confirmed that PMA-induced MMP-9 activity was significantly decreased by melittin, but not by apamin and phospholipase A(2). These data demonstrated that the expression of MMP-9 was abolished by melittin, the main component of bee venom.
CONCLUSION
Bee venom inhibits PMA-induced MMP-9 expression and activity by inhibition of NF-kappaB via p38 MAPK and JNK signaling pathways in MCF-7 cells. These results indicate that bee venom can be a potential anti-metastatic and anti-invasive agent. This useful effect may lead to future clinical research on the anti-cancer properties of bee venom.
民族药理学相关性
蜂毒在传统东方医学中被用于治疗炎症性疾病，如类风湿性关节炎，并缓解疼痛。
研究目的
本研究旨在阐明蜂毒对 MMP-9 表达的影响，并确定蜂毒在乳腺癌细胞侵袭和转移过程中缓解或预防 MMP-9 表达的可能机制。我们研究了 PMA 诱导的 MCF-7 细胞中 MMP-9 的表达和活性以及可能受影响的信号通路。
材料与方法
蜂毒购自韩国国立农业科学技术研究院。使用 Matrigel 侵袭实验、划痕愈合实验、酶谱分析、western blot 分析、电泳迁移率变动分析和荧光素酶基因分析进行评估。
结果
蜂毒抑制 PMA 诱导的 MCF-7 细胞的侵袭和迁移，以及 MMP-9 活性和表达，这些过程与肿瘤侵袭和转移有关。蜂毒特异性抑制 p38/JNK 的磷酸化，同时抑制 NF-κB 的蛋白表达、DNA 结合和启动子活性。磷酸化 ERK1/2 和 c-Jun 的水平没有变化。我们还研究了蜂毒中代表性单一成分蜂肽、蜂毒肽、蜂毒肽和 PLA2 对 MMP-9 的抑制作用。我们证实 PMA 诱导的 MMP-9 活性显著被蜂肽降低，但不是被蜂毒肽和磷脂酶 A2 降低。这些数据表明，蜂毒主要成分蜂肽可以消除 MMP-9 的表达。
结论
蜂毒通过 p38 MAPK 和 JNK 信号通路抑制 NF-κB，抑制 PMA 诱导的 MCF-7 细胞中 MMP-9 的表达和活性。这些结果表明，蜂毒可能是一种潜在的抗转移和抗侵袭剂。这种有益的作用可能会导致未来对蜂毒抗癌特性的临床研究。
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