| Abstract: | Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore investigated theeffects of barbigerone on all three in the B16F10 tumor model established in both zebrafish and mouse models,and explored underlying molecular mechanisms. In vitro, barbigerone inhibited B16F10 cell proliferation,survival, migration and invasion and suppressed human umbilical vascular endothelial cell migration, invasionand tube formation in concentration-dependent manners. In the transgenic zebrafish model, treatment with10μM barbigerone remarkably inhibited angiogenesis and tumor-associated angiogenesis by reducing blood vesseldevelopment more than 90%. In vivo, barbigerone significantly suppressed angiogenesis as measured by H andE staining of matrigel plugs and CD31 staining of B16F10 melanoma tumors in C57BL/6 mice. Furthermore,it exhibited highly potent activity at inhibiting tumor growth and metastasis to the lung of B16F10 melanomacells injected into C57BL/6 mice. Western blotting revealed that barbigerone inhibited phosphorylation of AKT,FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through theMEK3/6/p38 MAPK signaling pathway. These findings suggested for the first time that barbigerone could inhibittumor-angiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signalingpathway. The findings support further investigation of barbigerone as a potential anti-cancer drug. |
