ROZ与ATRA联合应用对MCF-7细胞诱导作用

Effects of combination of ROZ with ATRA on differentiation of MCF-7 cells

研究PPARγ激动剂罗格列酮(ROZ)与全反式维甲酸(ATRA)联合应用诱导MCF-7细胞发生分化和凋亡的作用,阐述PPARγ激活后的抗肿瘤作用和机制.采用克隆原形成实验测定两化合物对MCF-7细胞存活率的影响;采用诱导分化实验测定两化合物对MCF-7细胞分化的影响;并进一步应用RT-PCR分析两化合物对MCF-7细胞相关基因表达的影响.集落形成实验显示,两化合物联合应用后,能明显抑制MCF-7细胞的生长.诱导分化实验表明,ROZ在低剂量时促进MCF-7细胞的分化,而随着剂量的增加,分化作用减弱,与ATRA联合应用后,同样在低剂量时促进MCF-7细胞分化,并且出现脂滴的细胞数增加,脂滴增大,在高剂量时,分化作用亦有所减弱.RT-PCR结果表明,在两化合物的作用下,MCF-7细胞中PPARγ的表达升高,并使MCF-7细胞中与凋亡相关基因的表达发生变化.ROZ与ATRA联合应用具有协同作用,激活PPARγ,抑制MCF-7细胞增殖,诱导MCF-7细胞发生分化.

To study the effect of differentiation induction and apoptosis induction of combination of PPARy Agonist ROZ with ATRA in MCF -7 cells, and expound the antiOcancer activity and the possible molecular mechanisms of the combination. To detect the differentiation inducing effect by the combination. The colony formation experiment is used to detect the survival rate of MCF -7 cells, the relative gene expression is detected in MCF -7 cells by RT- PCR. Combination of ROZ with ATRA suppressed the colony formation markedly. The ability of differentiation is increased at low dose and decreased at high dose both by ROZ alone and combination of ROZ with ATRA in MCF - 7 cells. The data of RT - PCR showed that combination of ROZ with ATRA could induce the increase in PPARγ mRNA, and cause the changes of ERa,P53, Bcl - 2, bax,E-cad, integrin oL2 mRNA expression. The combination of ROZ and ATRA in MCF -7 cells demonstrated a cooperative effect on growth inhibition, differentiation induction and apoptosis induction.