【摘要】 目的:靶向性治疗是当前恶性肿瘤治疗的新方向,本研究观察针对核因子-κB(NF-κB)为靶序列的特异性环状哑铃寡聚脱氧核苷酸(CD-ODN)对人膀胱癌耐药细胞株多药耐药性的逆转作用。方法:脂质体介导法转染NF-κB-CD-ODN入人膀胱癌细胞株BIU-87及其多药耐药(MDR)亚株BIU-87/A,荧光素酶报告基因质粒检测不同处理组NF-κB活性的改变;RT-PCR、Western-blot、MTT法检测NF-κB-CD-ODN对2株细胞γ-GCSh mRNA表达、细胞内GSH水平及其对5种抗癌药物肿瘤细胞抑制率的变化。结果:NF-κB-CD-ODN转染48 h后,2株细胞内NF-κB活性、γ-GCSh mRNA的表达和GSH的水平均下降;同时5种抗癌药物对2株细胞的抑制率大部分都有提高。结论:γ-GCSh特异性的NF-κB-CD-ODN可通过降低细胞内GSH水平增强膀胱癌细胞对化疗的敏感性,逆转肿瘤细胞的耐药。更多还原

【Abstract】 Objective:Recently,the use of targeted intervention strategy represents a promising novel approach to neoplastic diseases.The purpose of this study was to investigate the reversal effect of specific circular dumbbell oligodeoxynucleotides(CD-ODNs),targeting the promoter domain nuclear factor kappa B(NF-κB) sequence,to the phenotype of multidrug resistance(MDR) in human bladder cancer cells.Methods:NF-κB-CD-ODNs and its’ mutant were transfected into human bladder cancer cell line BIU-87 and its drug resistance subline BIU-87/A by Lipofectamine.DNA binding activity of NF-κB was detected by luciferase reporter.The expression ofγ-GCSh mRNA,intracellular glutathione(GSH) levels and inhibitory effect of 5 chemotherapy agents were measured respectively by RT-PCR,Western blot and MTT assay 48h after transfection.Results:In comparison with CD-ODNs mutant,CD-ODNs inhibited significantly DNA binding activity of NF-κB and the expression ofγ-GCSh mRNA,decreased intracellular GSH content in BIU-87 and BIU-87/ A at 48h after transfections,and then increased two cell lines drug sensibility to most of chemotherapy agents.Conclusion:NF-κB-CD-ODNs targeting atγ-GCSh particularly can reverse in vitro the phenotype of MDR in bladder cancer cells by reducing the levels of intracellular GSH.更多还原