核因子κB靶向性圈套策略对膀胱癌细胞生长的影响

Effect of NF-κB decoy-circular dumbbell oligodeoxynucleotides on the growth inhibition of bladder cancer

目的观察核因子κB诱骗剂—环状哑铃寡核苷酸(CD-ODN)对膀胱肿瘤细胞增殖和凋亡的影响,探讨核因子κB环状圈套策略在膀胱肿瘤基因治疗中的作用。方法脂质体介导法瞬时转染CD-ODN及其突变体(CD-ODN-mut)入膀胱癌BIU-87细胞株,荧光素酶报告基因的方法检测不同处理组NF-κB活性的改变;MTT法、克隆形成试验检测各组细胞生长抑制情况;流式细胞仪检测细胞周期和早期凋亡。结果CD-ODN能明显降低膀胱癌细胞NF-κB活性,抑制膀胱癌细胞增殖和干细胞克隆形成,使细胞周期阻滞,促进膀胱癌细胞凋亡。结论CD-ODN可能通过阻断NF-κB信号通路来调控膀胱癌细胞的凋亡和周期,抑制细胞的增殖,促进其凋亡,为膀胱癌治疗提供新的思路。

[Objective] To investigate the effects of NF-κB decoy-circular dumbbell oligodeoxynucleotides （CD-ODN） on the proliferation and apoptosis of bladder cancer cells and evaluate the application of CD-ODN in the treatment of bladder cancer. [Methods] CD-ODN and CD-ODN-mut were transfected into bladder cancer cell line BIU87 by Lipofectamine. Luciferase reporter was applied for detecting NF-κB DNA binding activity. The inhibition of bladder cell proliferation was estimated by MTT and clone formation counting assay. Flow cytometry was applied to analyze the cell cycle and apoptosis. [Results] CD-ODN could remarkably suppress NF-κB DNA binding activation, inhibit the proliferation of bladder cancer cells and the formation of the tumor stem cell clones, block the cell cycle, facilitate the cell apoptosis. [Conclusions] CD-ODN could inhibit the proliferation of bladder cancer cells and induce their apoptosis possibly by blocking the NF-κB signaling pathway. It may be a new kind of treatment strategy for bladder cancer.