Danshensu has anti-tumor activity in B16F10 melanoma by inhibiting angiogenesis and tumor cell invasion.
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.
Zhang
Li-juan
LJ
Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Chen
Lei
L
Lu
Yin
Y
Wu
Jia-ming
JM
Xu
Bo
B
Sun
Zhi-guang
ZG
Zheng
Shi-zhong
SZ
Wang
Ai-yun
AY
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009994:Osmolar Concentration; D047368:Tumor Burden / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D007773:Lactates; D042442:Vascular Endothelial Growth Factors; C035055:3,4-dihydroxyphenyllactic acid; D053505:Matrix Metalloproteinases, Secreted