Danshensu, the major water-soluble component of Radix Salviae Miltiorrhizae (Danshen), is the basic chemical structure of various salvianolic
acids. This study was to evaluate the anti-
tumor activity of
danshensu in a series of in vitro and in vivo models. The effect of
danshensu on B16F10
melanoma cell and HUVEC proliferation were assessed by MTS assay, and cell invasion and migration were investigated by transwell chamber assay. The effect of
danshensu on angiogenesis was evaluated by HUVEC migration assay, tube formation assay and chick chorioallantoic membrane assay. The expression of MMP-2, -9 and
VEGF in B16F10
melanoma cell were detected by western blotting after
danshensu treatment. The role of
danshensu in
tumor metastasis in vivo was evaluated by spontaneous and experimental B16F10
melanoma metastasis model. Although
danshensu had no inhibitory effect on B16F10
melanoma cell and HUVEC proliferation, it significantly inhibited B16F10
melanoma cell invasion (at 0.05, 0.5, 5 microM) and migration (at 0.5, 5 microM). It also dramatically suppressed
VEGF-induced endothelial migration (at 0.5, 5 microM), tube formation in vitro (at 4, 20 microM) and new vessel formation in CAM in vivo (100 microg/egg).
Danshensu (at 5, 50 microM) significantly down-regulates
protein expression of MMP-2, -9 and
VEGF in B16F10
melanoma cell. In animal model,
danshensu (20, 40 mg/kg) also possessed inhibitory effect on lung
metastasis in spontaneous (46-day treatment) and experimental (23-day treatment) B16F10
melanoma metastasis model. All these results suggest that
danshensu has anti-
tumor activity by affecting on
tumor angiogenesis and
tumor invasion.