地塞米松增强L02细胞P-糖蛋白的表达作用机制的初步研究

Dexamethasone enhances P-glycoprotein expression in L02 cells via activation of PI3K / Akt signaling

目的探讨地塞米松对人正常肝细胞株L02细胞P-糖蛋白(P-gp)表达的影响,以及磷酸肌醇-3激酶(PI3K)/蛋白激酶B(Akt)途径在调控P-gp表达中的作用。方法采用Western blot检测体外培养L02细胞P-gp与Akt的表达水平,比较经地塞米松、PI3K/Akt酶抑制剂LY294002及两者联合处理24 h前后L02细胞P-gp表达水平的变化及地塞米松处理24 h前后L02细胞Akt表达水平的差异,分析L02细胞P-gp表达与PI3K/Akt表达之间的关系。结果 10μmol/L地塞米松刺激24 h后L02细胞P-gp及Akt表达水平较刺激前分别显著增加60.8%(P=0.026 7)和25.0%(P=0.035 8);L02细胞中P-gp表达水平与Akt表达水平之间呈显著正相关(Pearson系数=0.87,P<0.01);LY294002(20μmol/L)处理组L02细胞P-gp表达水平较对照组(未处理组)显著降低33.8%(P=0.018 4);地塞米松单独处理组和地塞米松与LY294002联合处理组L02细胞P-gp表达水平分别是对照组的(163.5±18.4)%和(130.1±22.0)%,两者间相差显著(P=0.031 3)。结论地塞米松可能通过激活PI3K/Akt途径诱导L02细胞P-gp增强表达。

Objective To determine the effects of dexamethasone （Dex） on the expression of P- glycoprotein （P-gp） in human normal liver cell line L02 cells, and investigate the role of phosphatidylinositol 3 kinase （PI3K） /protein kinase B （Akt） pathway in the regulation of P-gp expression. Methods The levels of P-gp expression were detected among untreated, Dex alone treated, PI3K/Akt inhibitor LY294002 alone treated, and both Dex and LY294002 treated L02 cells using Western blot assay. The levels of Akt expression were also detected in untreated and Dex treated L02 cells by Western blotting. The relationship of the expression of P-gp with that of Akt in L02 cells was analyzed. Results The expression levels of P-gp and Akt were significantly increased by 60.8% and 25.0% in L02 cells after treated with 10 μmol/L Dex for 24 h compared with those in untreated 1332 cells （ P = 0. 026 7, 0. 035 8 ）. The expression level of P-gp was positively correlated with the level of Akt in L02 cells （Pearson correlation coefficient = 0. 026 7, P 〈 0.01 ）. The level of P-gp was remarkedly decreased by 33.8% in LY294002 treated L02 cells than in untreated L02 cells （P =0.018 4）. The level of P-gp in Dex alone treated L02 cells accounted for （163.5± 18.4）% of untreated cells, significantly higher than that of 1332 cells treated by combination of Dex and LY294002 [ （130.1 ±22.0）%, P = 0.031 3 ]. Conclusion Dex may increase the expression level of P-gp in L02 cells by activation of PI3K/Akt signaling.