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多西他赛调控LS174T细胞血管生成因子的作用
Regulatory Effects of Docetaxel on Angiogenic Factors of LS174T Cell
【摘要】 目的 探讨多西他赛(Docetaxel)非细胞毒浓度下调控LS174T细胞血管生成因子的作用。方法 采用四唑盐比色实验(MTT)判定药物对 LS174T没有细胞毒作用的最大浓度。明胶酶谱分析、Western blot、逆转录聚合酶链反应(RT-PCR)等方法研究药物对其胶原酶活性、血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、基质金属蛋白酶 2和 9(MMP2和9)表达的作用。结果 判定1.0 ng/mL为药物对 LS174T细胞株没有细胞毒作用的最大浓度。与溶剂对照组相比较,0.1、0.5、1.0ng/mL多西他赛组对 LS174T细胞VFGF、bFGF、MMP2和MMP9的mRNA和蛋白表达均具有不同程度的下调作用,各组明胶酶的活性也呈下降趋势,各组间两两比较均具有显著性差异(P<0.01)。结论 非细胞毒浓度的多西他赛具有抑制LS174T细胞VEGF、bFGF、MMP2和9表达的作用,该药为有良好应用前景的血管生成抑制剂。
【Abstract】 Purpose To study the effects of non-cytotoxic concentrations of docetaxel on some important angiogenic factors of LS174T cells. Methods The non-cytotoxic concentration of docetaxel and the activity of gelatinase were determined with MTT and gelatin zymography respectively, the expression of VEGF ( vascular endothelial growth factor) , bFGF ( basic fibroblast growth factor) , MMP ( matrix metallopro-teinase)2 and 9 were investigated with RT-PCR and Western blot. Results The mean MTT relative A values of blank group, docetaxel solvent control group,0. 1,0. 2,0.5,1.0,2. 0,5.0,10. 0 ng/mL group were 1.000±0. 17,0.995±0. 23,0. 993±0. 16,0. 990±0. 12,0. 985±0. 13,0. 981±0.14, 0.848±0.16,0.657± 0.12,0. 485±0. 08 respectively; The maximum non-cytotoxic concentration of docetaxel on LS174T cells was 1.0 ng/mL. Compared with the solvent control group,0.1,0.5,1.0 ng/mL of doce-taxel could downregulate the expression of VEGF, bFGF, MMP 2 and 9 and suppress the activity of gelatinase (P<0.05). Conclusions Our study suggests that the non-cytotoxic concentrations of docetaxel has a strong antiangiogenic activity on LS174T cells, it may be a promising antiangiogenic agent.
【Key words】 docetaxel; LS174T cell; vascular endothelial growth factor; basic fibroblast growth factor; matrix metalloproteinase;
- 【文献出处】 复旦学报(医学版) ,Journal of Shanghai Medica(University) , 编辑部邮箱 ,2003年03期
- 【分类号】R73-36
- 【被引频次】4
- 【下载频次】105