【摘要】 目的检测6种倍半萜内酯化合物对人乳腺癌细胞增殖活性的影响,并探讨其可能的作用机制。方法人乳腺癌细胞MCF-7和人乳腺癌脑转移细胞KT分别与6种倍半萜内酯化合物作用48h,噻唑蓝比色法检测细胞存活率;珊塔玛内酯10μmol/L作用MCF-7细胞24h,双荧光素酶报告基因检测系统检测细胞内Bax报告基因和激活T细胞核因子(nuclear factor of activated T cells,NFAT)报告基因的表达。结果异土木香内酯和珊塔玛内酯对2种人乳腺癌细胞均显示极强的抑制作用,呈剂量依赖性,半数抑制浓度仅为4.40μmol/L和4.57μmol/L,而其他试验用倍半萜内酯即使在100μmol/L高浓度下,对人乳腺癌肿瘤细胞的增殖不显示抑制活性;珊塔玛内酯可显著诱导MCF-7细胞内Bax和NFAT报告基因表达(P<0.01)。结论异土木香内酯和珊塔玛内酯对2种人乳腺癌细胞均显示极强的抑制作用;珊塔玛内酯对人乳腺肿瘤细胞增殖的抑制作用可能是通过诱导MCF-7细胞的Bax表达,使NFAT激活,导致线粒体膜的转移渗透孔通透性改变,使细胞色素C从线粒体释出,活化caspase 9,进而激活caspase 3,导致细胞凋亡的发生所致。更多还原

【Abstract】 Objective To detect the anti-human breast cancer cells effects of six sesquiterpenoid lactones isolated from Inula helenium,and to explore its mechanism.Methods The anti-human breast tumor effects of six sesquiterpenoid lactones were investigated using human breast cancer cells(MCF-7 and KT).The cell viabilities were examined by MTT assay.MCF-7 cells were transiently cotransfected by pGBax-Luc and NFAT-Luc reporter plasmid and SV-40-Rluc plasmid.The effects of santamarine of luciferase activity expression were detected by dual-luciferase reporter assays.Results Isoalantolactone and santamarine exhibited significantly anti-growth activities to human breast cancer,and half maximal inhibitory concentration value of MCF-7 and KT cell were 4.40μmol/L and 4.57μmol/L exposure.Other sesquiterpenoid lactones demonstrated weak anti-growth activities to cell lines even in the concentration of more than 100μmol/L.The reporter gene of pGBax-Luc and NFAT-Luc were observed in response to santamarine.Conclusion Isoalantolactone and santamarine have significant anti-growth activities in human breast cancer cells.The possible mechanism of the anti-human breast tumor activity of santamarine is through caspase-3 and caspase-9 activation inducing cell apoptosis.更多还原