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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。
OBJECTIVE: Targeted therapy is a new direction for the treatment of malignant tumors. In this study, we observed the effect of specific cyclic dumbbell oligodeoxynucleotides (CD-ODNs) directed against nuclear factor-κB (NF-κB) Reversal effect of multidrug resistance in bladder cancer resistant cell line. Methods: Human bladder cancer cell line BIU-87 and its multidrug-resistant (MDR) subunit BIU-87 / A were transfected with NF-κB-CD-ODN by lipofectamine. Luciferase reporter plasmids The effect of NF-κB-CD-ODN on the expression of γ-GCSh mRNA and the level of intracellular GSH in the two cell lines were detected by RT-PCR, Western-blot and MTT assay. Changes in tumor cell inhibition rate. RESULTS: After 48 hours of NF-κB-CD-ODN transfection, the activity of NF-κB, the expression of γ-GCSh mRNA and the level of GSH in both cells decreased. At the same time, the inhibitory rates of 5 kinds of anticancer drugs on 2 cells Most have improved. CONCLUSION: γ-GCSh-specific NF-κB-CD-ODN can enhance the sensitivity of bladder cancer cells to chemotherapeutic treatment and reduce the drug resistance of tumor cells by decreasing intracellular GSH level.