DT-13,a saponin of dwarf lilyturf tuber,exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells

AIM:To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action.METHODS:MDA-MB-435 cell proliferation,migration,and adhesion were performed to assess the anticancer activity of DT-13,a saponin from Ophiopogon japonicus,in vitro.In addition,the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice;mRNA levels of vascular endothelial growth factor(VEGF),C-C chemokine receptor type 5(CCR5) and hypoxia-inducible factor 1(HIF-1) were evaluated by real-time quantitative PCR;and CCR5 protein levels were detected by Western blot assay.RESULTS:At 0.01 to 1 molL-1,DT-13 inhibited MDA-MB-435 cell proliferation,migration,and adhesion significantly in vitro.DT-13 reduced VEGF and CCR5 mRNAs,and decreased CCR5 protein expression by down-regulating HIF-1.In addition,DT-13 inhibited MDA-MB-435 cell lung metastasis,and restricted tumor growth slightly in vivo.CONCLUSION:DT-13 inhibited MDA-MB-435 cell proliferation,adhesion,and migration in vitro,and lung metastasis in vivo by reducing VEGF,CCR5,and HIF-1 expression.