Kunze Doreen, Wuttig Daniela, Fuessel Susanne, Kraemer Kai, Kotzsch Matthias, Meye Axel, Grimm Marc-Oliver, Hakenberg Oliver W, Wirth Manfred P
Department of Urology, Technical University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany.
Anticancer Res. 2008 Jul-Aug;28(4B):2259-63.
The knockdown of XIAP, BCL2 and BCL-X(L) by siRNAs represents a promising treatment option for bladder cancer (BCa) since the overexpression of antiapoptotic genes is often associated with tumor progression and treatment resistance.
EJ28 BCa cells were transfected with siRNAs--separately and combined--followed by analysis of target expression, viability, clonogenic survival, apoptosis and cell cycle. Furthermore, a possible chemosensitization by siRNA pretreatment was investigated.
The siRNA-mediated inhibition of these targets--either separately or combined--reduced the targets' expression, reduced cell growth and sensitized cells to a subsequent chemotherapy.
Since tumor cells may bypass the inhibition of a single gene by changing their expression profile, e.g. switch from BCL2 to BCL-X(L), the combined knockdown of multiple genes of the same pathway might be more effective in killing cancer cells. The siRNAs used represent appropriate tools for this aim since they reduced their targets' expression significantly and long-lastingly.
由于抗凋亡基因的过表达常与肿瘤进展和治疗耐药相关，因此通过小干扰RNA（siRNA）敲低X连锁凋亡抑制蛋白（XIAP）、B细胞淋巴瘤2（BCL2）和B细胞淋巴瘤-extra-large（BCL-XL）是一种有前景的膀胱癌（BCa）治疗选择。
用siRNA分别或联合转染EJ28膀胱癌细胞，随后分析靶标表达、细胞活力、克隆形成存活、凋亡和细胞周期。此外，研究了siRNA预处理可能产生的化学增敏作用。
siRNA介导的对这些靶标的抑制，无论是单独还是联合抑制，均降低了靶标表达，减少了细胞生长，并使细胞对后续化疗敏感。
由于肿瘤细胞可能通过改变其表达谱来绕过对单个基因的抑制，例如从BCL2转换为BCL-XL，因此同一信号通路多个基因的联合敲低可能在杀死癌细胞方面更有效。所使用的siRNA是实现这一目标的合适工具，因为它们能显著且持久地降低其靶标的表达。
Zotero 插件