Inhibition of invasion and experimental metastasis of murine melanoma cells by Ipomoea obscura (L.) is mediated through the down-regulation of inflammatory mediators and matrix-metalloproteinases.

摘要

In this study, we tested the anti-metastatic activity of Ipomoea obscura extract and elucidated its underlying mechanisms by in vitro system using B16F-10 melanoma cells and in vivo experimental lung metastasis model. I. obscura suppressed proliferation, invasion and migration of highly metastatic B16F-10 melanoma cells in vitro. I. obscura could also decrease transcription factors such as nuclear factor kappaB (NF-kappaB) and activator protein (AP-1) in B16F-10 melanoma cells. Administration of I. obscura resulted significant suppression of B16F-10 melanoma induced tumor nodule formation and enhanced the survival of tumor-bearing mice. The level of various biochemical parameters associated with lung metastasis were also found to be decreased by the I. obscura treatment. A significant down regulation in the expression of inflammatory mediators such inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), pro-inflammatory cytokines related to tumor metastasis was observed by the treatment with I. obscura. Higher expression levels of pro-metastatic genes such as matrix metalloproteinase (MMP-2 and 9), was observed in the metastatic group, but these were down-regulated by the treatment with I. obscura. The endogenous MMP inhibitor tissue inhibitor of metalloproteinases (TIMP) was found to be up-regulated by I. obscura treatment. Our results indicate that the anti- invasive and antimetastatic effect of I. obscura is mediated at least in part by reduced expression of inflammatory mediators by inhibiting NF-kappaB signaling with their downstream targets iNOS, COX-2 and pro-inflammatory cytokine and also by inhibiting MMP-9 and MMP-2.