APPLICATION OF BGL-2 ANTISENSE OLIGO-DNA FOR GENE THERAPY TO UROLOGICAL CANCER.

我们先前已经表明，Bcl-2表达是膀胱移行细胞癌（TCC）的负预后因子，并且表达高水平Bcl-2的TCC细胞系对阿霉素引发的细胞凋亡具有抗性。在此，我们检测了反义寡核苷酸介导的Bcl-2表达下调及其对T24细胞对ADM治疗敏感性的影响。用20 μM的bcl-2反义PODN处理T24细胞后，Bcl-2蛋白水平降低。与阿霉素联合给药导致协同细胞毒性，伴随着DEVD特异性caspase活性增加2.4倍。这一发现为Bcl-2表达可能是维持TCC耐药性的关键提供了证据。bcl-2反义寡核苷酸可能是治疗肿瘤的有效手段。克服高度恶性TCC的耐药性，

We have previously shown that Bcl-2 expression was negative prognostic factor in transitional cell cancer (TCC), and that TCC cell lines expressing high levels of Bcl-2 are resistant to Adriamycin triggered apoptosis. Here we examined antisense oligonucleotide - mediated downregulation of Bcl-2 expression and its effect on sensitivity to ADM treatment in T24 cells. Treatment of T24 cells with 20 μM of bcl-2 antisense PODN reduced the Bcl-2 protein level. Combined administration with Adriamycin resulted in synergistic cytotoxicity, accompanied with a 2.4-fold increase in DEVD-specific caspase activity. The finding provides evidence that Bcl-2 expression may be critical for maintaining the drug resistance of TCC. bcl-2 antisense PODN might be useful means for. overcoming drug resistance in highly malignant TCC,