文档介绍：PPAR-γ抑制剂T0070907对人鼻咽癌细胞的生长抑制作用
作者:孙月丽吴明玮曾昭蕾孙健蔡于琛冼励坚赵擎宇
【摘要】【目的】探讨PPAR-γ选择性抑制剂T0070907影响鼻咽癌(NPC)细胞体外生长的作用机制。【方法】通过RT-PCR和Western blotting检测PPAR-E2、HONE1、SUNE1和5-8F)中mRNA和蛋白水平的表达;MTT法检测T0070907对NPC细胞生长情况的影响;流式细胞术和Western blotting检测T0070907对NPC细胞的细胞周期和细胞周期相关蛋白表达的影响。【结果】 PPAR-γ在5株NPC细胞中均有表达;T0070907对NPC细胞株有明显生长抑制作用,并呈浓度、时间依赖性;E2后,G2/M期细胞比例则逐渐增加,且随着处理浓度的增加而增加,各组间差异有统计学意义(P < )。此外,随着T0070907处理浓度的增加,NPC细胞的细胞周期相关蛋白Cyclin A、Cyclin B1、Cdc2、Cdk2蛋白的表达逐渐下降,无活性的pCdc2蛋白表达则逐渐增强。【结论】 PPAR-γ抑制剂T0070907能够抑制NPC细胞PPAR-γ的蛋白表达,并通过对细胞周期相关蛋白Cyclin A、Cyclin B1、Cdc2、Cdk2、pCdc2等蛋白的调控导致细胞周期G2/M期阻滞,从而抑制NPC细胞的生长。
【关键词】 PPAR-γ; 鼻咽癌; T0070907; 细胞周期; G2/M期
Abstract: 【Objective】 PPAR-γ(peroxisome proliferator-activated receptor-γ) antagonists have been documented to induce cancer cell proliferation inhibition and apoptosis. In the present study PPAR-γ’s effect on cell growth of NPC cell lines and the possible mechanism was investigated via its selective
inhibitor T0070907. 【Methods】 PPAR-γ mRNA and protein expression in five human NPC cell lines (CNE1, CNE2, HONE1, SUNE1, and 5-8F) was detected with RT-PCR and Western blotting analysis. NPC cells growth inhibition by T0070907 was measured by MTT assay, and cell cycle arrest of NPC cells treated with T0070907 was assayed by fluorescence-activated cell sorter (FACS) analysis. Cell cycle-associated protein expression was detected by Western blotting. 【Results】 PPAR-γ was expressed both at mRNA and protein levels in five NPC cell lines. NPC cells’ proliferation was significantly inhibited by T0070907, and the growth inhibition was dose- and time-dependent. CNE1 E2 cells treated for 48 h with T0070907 markedly accumulated dose-dependently in the phase of G2/M, while they differed significantly (P < ) in the phase as well. T0070907 suppressed expression of cell cycle-related proteins including Cyclin A, Cyclin B1, Cdc2, and Cdk2 but increased pCdc2 expression. 【Conclusion】 PPAR-γ inhibitor T0070907 could induce proliferation inhibi