Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase-independent pathway
Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase-independent pathway
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DOI：
10.1002/jcb.21836
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发表时间：
2008-10-01
影响因子：
4
通讯作者：
Rivarola, Viviana A.
中科院分区：
文献类型：
--
作者：
Croci, Diego O.;Cogno, Ingrid S.;Rivarola, Viviana A.
由于Survivin在大多数肿瘤中的选择性过表达，其被认为是肿瘤治疗中有吸引力的靶点。这种蛋白质的上调表达与肿瘤分级增加、复发风险增加和癌症患者存活率降低相关。在这项研究中，我们评估了两种生存素特异性小干扰RNA（siRNA）构建体抑制T47 D人乳腺癌细胞生长的功效。siRNA转染后，T47 D细胞显示出增殖和存活的显著降低，表现出明显的凋亡迹象。与靶向外显子4的pSil_30相比，靶向外显子1的pSil_1对细胞生长表现出更强的抑制作用，并增加细胞凋亡。线粒体凋亡诱导因子（AIF）的易位介导的细胞凋亡，而没有观察到的caspase-3激活和Bid切割的变化。因此，使用siRNA策略沉默生存素表达代表了选择性调节人乳腺癌细胞的存活和生长的合适的治疗方法。
Survivin is recognized as an attractive target in cancer therapy because of its selective overexpression in the majority of tumors. Upregulated expression of this protein correlates with increased tumor grade, recurrence risk and decreased cancer patients survival. In this study, we assessed the efficacy of two survivin-specific small interfering RNA (siRNA) constructs to inhibit T47D human breast cancer cell growth. After siRNA transfection, T47D cells showed a significant reduction in proliferation and survival exhibiting clear signs of apoptosis. pSil_1 that targeted exon 1 exhibited a stronger inhibitory effect on cell growth, and increased cell apoptosis compared to pSil_30 that targeted exon 4. Cell apoptosis was found to be mediated by translocation of the mitochondrial apoptosis inducing factor (AIF), while no changes were observed in caspase-3 activation and Bid cleavage. Thus, silencing survivin expression using siRNA strategies represents a suitable therapeutic approach to selectively modulate the survival and growth of human breast cancer cells.