淋巴细胞性白血病细胞被诱导对地塞米松耐药后对糖皮质激素受体的影响

bstract：Objective: To establish CEM-C7 cell model of dexamethasone （DEX） induced resistance and analyze the changes in cell phenotype in order to demonstrate the possible mechanism of acquired glucocorticoid resistance and to help to determine the duration and dose of glucocorticoid treatment. Methods: GC sensitive CEM-C7 cells was treated with DEX and then the apoptosis rate measured by Annexin V-FITC/PI kit was compared with the parental cells until the resistant line CEM-C7R was stably established. We use Real-time RT-PCR, Laser confocal cell immunofluorescence technique, western blotting to analyze the difference in glucocorticoid receptors (GR) expression between CEM-C7 and CEMDexamethasone induced resistance in acute T lymphatic leukemia and its impact on glucocorticoid receptors-C7R. Results: GC resistance of CEM-C7R cells could be induced by chronic treatment with 10 nmol/L DEX for 4 weeks. Cell survival rate could reach 92.30±2.51% (p＜0.01). Total mRNA expression of GR, the mRNA expression of GRα、GRγ及GRρwere significantly reduced in CEM-C7R, compared with its parental counterpart. Conclusion: Low-dose DEX could induce resistance in CEM-C7 cell line without causing mutations in NR3C1 gene. The relative mRNA expressions of total GR, GRα、GRγ、GRρ and the protein expression of GR were significantly lower in resistant cell line than its parental counterpart., indicating that unknown mechanism may function at transcription level or pre-translation level of NR3C1 gene to cause acquired glucocorticoid resistance in CEM-C7 cell line.