Fuessel Susanne, Herrmann Jana, Ning Shuangli, Kotzsch Matthias, Kraemer Kai, Schmidt Uta, Hakenberg Oliver W, Wirth Manfred P, Meye Axel
Department of Urology, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
Cancer Lett. 2006 Feb 8;232(2):243-54. doi: 10.1016/j.canlet.2005.02.027.
Survivin is known to be overexpressed in numerous tumor types including human bladder cancer and to cause resistance to radiation and chemotherapy. Therefore, we tested the antisense oligodeoxynucleotide AS-SVV286 and the small interfering RNA si-SVV284 to down-regulate survivin in the BCa cell lines EJ28 and 5637 thereby acting as sensitizers for chemotherapy. Pretreatment with these inhibitors followed by chemotherapy caused an enhanced decrease in cell viability. The observed reduction in cell counts associated with increased rates of apoptosis paralleled the degree of reduction of survivin expression that was achieved more efficiently by the siRNA than by the AS-ODN. Nevertheless, both therapy approaches in combination with all tested chemotherapeutics provoked a remarkable inhibition of viability and may serve as suitable additive tools for chemosensitization of bladder cancer cells.
已知生存素在包括人类膀胱癌在内的多种肿瘤类型中过度表达,并导致对放疗和化疗产生抗性。因此,我们测试了反义寡脱氧核苷酸AS-SVV286和小干扰RNA si-SVV284,以下调膀胱癌细胞系EJ28和5637中的生存素,从而作为化疗的增敏剂。用这些抑制剂预处理后再进行化疗,可增强细胞活力的降低。观察到的细胞计数减少与凋亡率增加相关,这与生存素表达的降低程度平行,其中siRNA比反义寡脱氧核苷酸更有效地实现了生存素表达的降低。然而,两种治疗方法与所有测试的化疗药物联合使用时,均能显著抑制细胞活力,可作为膀胱癌细胞化学增敏的合适辅助工具。