目的观察过氧化物酶体激活物活化受体γ(PPARγ)的配体土槿乙酸(PLAB)联合维甲类X受体α(RXRα)的配体9-顺式维甲酸(9cisRA)对白血病细胞生长的影响。方法应用MTT法检测细胞生长抑制率,流式细胞术和Hoechst33342/PI染色分析HL-60细胞凋亡及细胞周期变化,RT—PCR检测PPAR7和RXRdmRNA表达。结果HL60细胞系上有PPARγ和RXRα的表达,经配体联合作用后能明显抑制细胞生长,呈剂量依赖关系;细胞出现明显凋亡形态学改变和亚G1峰;PPARγ和RXRdmRNA表达明显增强。结论PLAB能显著增强9~cisRA对HL-60细胞的生长抑制作用,其机制与凋亡诱导效应有关。
Objective To study the effects of pseudolaric acid B (PLAB) combined with 9-cis retinoic acid (9-cis RA) on the growth inhibition of human leukemia cells. Methods Human leukemia cells of the line HL-60 were cultured and then divided into 4 groups: control group; 9-cis RA group(9-cis RA, a RXRa ligand, was added); PLAB group (PLAB, a PPAR7 ligand, was added) and combination group(9 cis RA and PLAB,were both added). 96 h later the cell growth inhibition rate was detected by MTT assay. Flow cytometry and Hoecbst33342/PI staining were used to detect the cell cycle and apoptosis. RT-PCR was used to detect the mRNA expression of RXRα and PPART. Results PPAR7 and RXRα were ex pressed in HL-60 cell line. The cell proliferation was inhibited by PLAB combined with 9 cis RA in dose- dependently manner. HL60 cells exhibited typical apoptotic morphological alteration and sub-G1 peak. PLAB combined with 9-cis RA significantly enhanced the mRNA expression of RXRα and PPART. Conclusion PLAB enhances the growth inhibitiory effect of 9-cis RA on human leukemia cells by the mechanism of induction of apoptosis.