地塞米松诱导人肺腺癌A549细胞对紫杉醇耐药性及Bcl-xL基因表达的影响

Influence of lung adenocarcinoma A549 cells induced by dexamethasone on the drug resistance of PTX and expression of Bcl-xL gene

目的观察紫杉醇(PTX)干预不同浓度地塞米松(DEX)预处理人肺腺癌A549细胞后的耐药情况和Bcl-xL基因及蛋白表达变化,探讨DEX诱导A549细胞对PTX产生耐药的分子机制。方法采用四甲基偶氮唑蓝比色法(MTT法)测定不同浓度PTX作用于A549细胞后的细胞存活率,筛选出PTX的半数抑制浓度(IC50);用不同浓度DEX预处理A549细胞后,再给予不同浓度PTX作用于A549细胞,用MTT法测定细胞存活率,逆转录-聚合酶链反应和蛋白质印迹法检测细胞中Bcl-xL基因和蛋白的表达。结果不同浓度DEX预处理A549细胞后能诱导其对PTX产生耐药,细胞存活率随DEX浓度的增加而增高,Bcl-xL基因和蛋白表达水平随DEX浓度的增加而增高。结论 DEX能诱导A549细胞对PTX产生耐药,其机制可能与DEX诱导A549细胞抗凋亡Bcl-xL基因表达增加有关。

Objective To observe the changes of the drug resistance of lung adenocarcinoma A549 cells and the expres-sion of mRNA and protein of Bcl-xL in human lung adenocarcinoma A549 cell after dexamethasone（DEX） pretreatment in dif-ferent concentrations and intervention with paclitaxel（PTX）,and to explore the molecular mechanism of DEX-induced A549 cell to the drug resistance of PTX. Methods The cell viability rate of lung adenocarcinoma A549 cells was determined by MTT assay after treatment of different concentrations of PTX,and to screen the half inhibitory concentration（IC50） of PTX. The cell viability rate of A549 cells which pretreated with different concentrations of DEX and different concentrations of PTX was determined by MTT assay,and the expression level of mRNA and protein of Bcl-xL in the A549 cells were determined by reverse transcriptase-poly merase chain reaction（RT-PCR） and Western blotting. Results After being pretreated with DEX in different concentrations, A549 cells were induced to resist to PTX,and the rate of resistance increased gradually with the increasing concentrations of DEX and the expression level of Bcl-xL gene and protein also increased gradually with the increasing of DEX concentrations. Conclu-sions DEX can induce resistance to PTX in lung adenocarcinoma A549 cells ,whose mechanism might be involved in increase of Bcl-xL gene（anti-apoptosis gene） in DEX-induced lung adenocarcinoma A549 cells.