Simultaneous siRNA-mediated knockdown of antiapoptotic BCL2, Bcl-xL, XIAP and survivin in bladder cancer cells.
Simultaneous siRNA-mediated knockdown of antiapoptotic BCL2, Bcl-xL, XIAP and survivin in bladder cancer cells.
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DOI：
10.3892/ijo.2012.1549
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发表时间：
2012-10
影响因子：
5.2
通讯作者：
Fuessel S
中科院分区：
文献类型：
--
作者：
Kunze D;Kraemer K;Erdmann K;Froehner M;Wirth MP;Fuessel S
膀胱癌（BCa）是世界上第九大最常见的恶性肿瘤。尽管采用手术和化疗进行了强化治疗，但BCa患者的预后，特别是晚期患者的预后很差。逃避细胞凋亡的能力是癌细胞的标志。由于抗凋亡基因BCL 2、Bcl-xL、XIAP和生存素在BCa组织中频繁上调，因此它们的组合siRNA介导的敲除可能比单一抑制一个靶点更有效地降低BCa生长。针对每个靶标，选择两种siRNA，其特异性降低EJ 28和J82 BCa细胞中其适当靶标的mRNA和蛋白质水平。抑制生存素引起所有单靶点治疗的最强抗增殖作用，例如细胞计数减少50%。同时靶向所有四种抗凋亡基因下调所有靶标的表达水平，并介导细胞活力和细胞计数的显著降低以及凋亡的诱导。在EJ 28细胞中，BCL 2，Bcl-xL，XIAP和生存素的联合敲低导致凋亡率增加2.5倍，细胞活力降低40%。因此，同时敲除抗凋亡BCL 2、Bcl-xL、XIAP和生存素可能代表膀胱癌的有希望的治疗选择。
Bladder cancer (BCa) represents the ninth most common malignancy worldwide. Despite intensive treatment with surgery and chemotherapy the prognosis for BCa patients particularly at advanced stages is poor. The ability to evade apoptosis is a hallmark of cancer cells. Since the antiapoptotic genes BCL2, Bcl-xL, XIAP and survivin are frequently upregulated in BCa tissues, their combined siRNA-mediated knockdown might be more potent in decreasing BCa growth than the single inhibition of one target. Against each target two siRNAs were selected that specifically reduced the mRNA and protein levels of their appropriate target in EJ28 and J82 BCa cells. Inhibition of survivin provoked the strongest antiproliferative effect of all single target treatments, for example cell counts decreased by 50%. Simultaneous targeting of all four antiapoptotic genes downregulated expression levels of all targets and mediated significant reductions in cell viability and cell counts as well as induction of apoptosis. In EJ28 cells, combined knockdown of BCL2, Bcl-xL, XIAP and survivin caused a 2.5-fold enhancement in apoptosis rate and reduced cellular viability by 40%. Therefore, simultaneous knockdown of antiapoptotic BCL2, Bcl-xL, XIAP and survivin may represent a promising treatment option for bladder cancer.
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