Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital , Taipei, Taiwan.
J Agric Food Chem. 2012 Dec 26;60(51):12451-7. doi: 10.1021/jf300964f. Epub 2012 Dec 13.
Silibinin is a flavonoid with antihepatotoxic properties and pleiotropic anticancer capabilities. This study investigated silibinin inhibition of cell invasion by down-regulating matrix metalloproteinase-2 (MMP-2) expression, via attenuation of activator protein-1 (AP-1) in IL-6-stimulated LoVo colon cancer cells. Western blot data showed that the expression of MMP-2 protein was reduced 1.6- or 1.7-fold over the control by treatment with silibinin or JNK inhibitor in the models. Similar results were revealed in zymography and confocal microscopy. Pretreatment with silibinin also abolished the binding activity of AP-1 and MMP-2 promoter activity via AP-1 binding, as observed by EMSA and luciferase assay. Finally, a [(3)H]-thymidine incorporation proliferation assay and cell migration assay demonstrated that silibinin inhibited IL-6-stimulated LoVo cell proliferation and invasion. Taken together, these data indicated that silibinin inhibits LoVo cell invasion with the reduction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel antimetastatic application for silibinin in colon cancer chemoprevention.
水飞蓟宾是一种具有抗肝毒性和多种抗癌作用的黄酮类化合物。本研究探讨了水飞蓟宾通过抑制 IL-6 刺激的 LoVo 结肠癌细胞中激活蛋白-1（AP-1），下调基质金属蛋白酶-2（MMP-2）表达，抑制细胞侵袭的作用。Western blot 数据显示，与对照组相比，水飞蓟宾或 JNK 抑制剂处理后 MMP-2 蛋白表达降低 1.6 或 1.7 倍。在明胶酶谱和共聚焦显微镜下也得到了类似的结果。通过 EMSA 和荧光素酶测定，水飞蓟宾预处理还通过 AP-1 结合消除了 AP-1 和 MMP-2 启动子活性的结合活性。最后，[（3）H]-胸苷掺入增殖试验和细胞迁移试验表明，水飞蓟宾抑制了 IL-6 刺激的 LoVo 细胞增殖和侵袭。总之，这些数据表明，水飞蓟宾通过抑制 AP-1 结合活性降低 MMP-2 表达，抑制 LoVo 细胞侵袭，提示水飞蓟宾在结肠癌化学预防中有新的抗转移应用。
