PPARγ和RXRα配体联用对白血病细胞生长作用机制的研究

Up-expression of peroxisome proliferator-activated receptor-γ and of retinoid X receptor-α enhances the inhibitory effect on leukemia cells

目的研究过氧化物酶体增生物活化受体（PPARγ）和维甲类X受体（RXRα）在人类白血病细胞（HL-60、K562、U937）中的表达及其对配体作用的反应。方法采用MTT法检测细胞生长；半定量RT-PCR法检测PPARγ和RXRα mRNA的表达。结果PPARγ和RXRα在HL-60细胞中有较强表达，在K562、U937细胞中表达较弱。PPARγ的配体土槿乙酸（PLAB）能显著抑制3株细胞的生长，PLAB与RXRα的配体9-顺式维甲酸（9-cisRA）联合作用时，与PLAB单独作用比较，对受体高表达的HL-60细胞抑制作用增强较明显（P〈0．05），但对K562、U937的作用增强不明显（P〉0．05）。PLAB和9-cisRA分别上调HL-60细胞PPARγ和RXRα的表达，且联合作用组显著高于单独作用组（P〈0．05）。结论在HL-60、K562、U937细胞中，HL-60细胞PPARγ和RXRα表达最强，这对配体发挥作用可能是必需的，配体发挥的抑制细胞生长的效应可能与其介导的信号途径有关。

Objective To investigate the relationship between the expression of peroxisome proliferators-activated recepter-γ （PPARγ） and retinoid X receptor-α （RXRα） and the inhibitory effect of PLAB, ligand of PPARγ and 9-cisRA, ligand of RXRα on growth of human leukemia cell lines （HL-60, K562 and U937） in vitro. Methods The antiproliferative effect was evaluated by MTT assay. The mRNA expression of PPARγ and RXRα was semi-quantified by RT-PCR. Results PPARγ and RXRα mRNA was both expressed in HL-60, K562 and U937 cells, and the expression in HL-60 was significantly higher than that in K562 and U937. The significant inhibitory effect on the growth of HL-60 cells was observed in K562 and U937 cells. The combination group showed more inhibitory effect in HL-60 cells than PLAB alone（P 〈0.05）. PLAB significantly up-regulates the expression of PPARγ in HL-60 cells, the expression of PPARγ and RXRα were higher in combination group than PLAB alone （P 〈0.05）. Conclusion The expression of PPARγ and RXRα in HL-60, K562 and U937 cell lines predicts their response to PLAB and 9-cisRA treatment, and the inhibitory effect is different in these three kinds of cell lines, which may be related to their ligands - mediated signal pathway.