罗格列酮与ATRA联合诱导MCF-7细胞加速性细胞衰老的研究

Studies on accelerated cellular senescence by ROZ in combination with ATRA in MCF-7 cells

目的探讨PPARγ激动剂罗格列酮(ROZ)与全反式维甲酸(ATRA)联合作用于p53野生型人乳腺癌MCF-7细胞能否增强衰老诱导作用,并进一步研究p53、p21基因在此过程中的作用。方法MTT法检测ROZ、ATRA及两者联合应用对MCF-7细胞增殖能力的影响。采用RT-PCR测定药物对p53、p21基因水平的影响。结果ATRA显著能增强ROZ对MCF-7细胞的生长抑制作用,且两者呈协同作用。两者在低于诱导细胞凋亡的剂量下可诱导MCF-7细胞呈衰老样表型,维持细胞衰老状态。ATRA能增强ROZ诱导MCF-7细胞衰老的作用。ROZ与ATRA联合诱导的MCF-7衰老过程中,p53、p21mRNA表达升高。结论ATRA能增强ROZ对MCF-7细胞的生长抑制作用及衰老诱导作用,p53、p21基因参与了ROZ与ATRA联合诱导细胞衰老的调控。

Objective To study whether ATRA can increase the effect of inducing accelerated cellular senescence （ACS） by ROZ in p53 wild-type cancer line MCF-7 cells and to study the role of p53 and p21 in the process. Methods MTT assay was used to examine the growth activities on MCF-7 cells, the cooperative effects of ROZ and ATRA on inhibiting the growth of MCF -7 cells were analyzed. Western Blot and RT-PCR was used to detect the expression level of p53,p21. Results Enhanced antiproliferative effects were obtained when MCF-7 cells were treated by the combination of ROZ with ATRA. The combination induced accelerated celluar senescence synergistically. The expresson level of p53 ,p21 ATRA can reinforce the susceptibility were unregulated after incubation by to accelerated cellular senescence in by ROZ, and p53, p21 played an important role in the process. drugs. MCF-7 cells induced