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Background In multiple myeloma (MM),bone marrow angiogenesis parallels tumour progression and correlates withdisease activity.Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo.In thisstudy,we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol onsome important angiogenic factors of RPMI 8226 cells.Methods RPMI 8226 cells were cocultured with human umbilical vein endothelial cells(HUVECs) to evaluate theeffects of myeloma cells on angiogenesis.The RPMI 8226 cells were treated with various concentrations of resveratrol(6.25-50.00 μmol/L) for different times (12-72 hours).Reverse transcriptase polymerase chain reaction(RT-PCR) wasused to assay vascular endothelial growth factor(VEGF),basic fibroblast growth factor (bFGF),metalloproteinases(MMP)-2 and MMP-9 mRNA.Gelatin zymography was used to analyze MMP-2 and MMP-9 activity.VEGF and bFGFproteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA).Results Cell proliferation,migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226cells.Resveratrol inhibited proliferation,migration and tube formation of HUVECs cocultured with myeloma cells in adose dependent manner.Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity.Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner.Furthermore,decreased levels of VEGF,bFGF,MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrolconfirmed its antiangiogenic action at the level of gene expression.Conclusions Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF,bFGF,MMP-2 and MMP-9.Resveratrol may be a potential candidate for the treatment of multiple myeloma.Chin Med J 2007;120(19):1672-1677
Background In multiple myeloma (MM), bone marrow angiogenesis parallels tumor progression and correlates with activityase. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. This thisudy, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol onsome important angiogenic factors of RPMI 8226 cells. Methods RPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25-50.00 (12-72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quant Results of Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in adosependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Future, decreased levels of VEGF, bFGF, MMP-2 and MMP- treated with various concentrations of resveratrolconfirmed its antiangiogenic action at the level of gene expression. Conclusions Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9.Resveratrol may be a potential candidate for the treatment of multiple myeloma. Chin Med J 2007; 120 (19): 1672-1677