Down-regulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth
Down-regulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth
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DOI：
10.1038/sj.neo.7900091
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发表时间：
2000-05-01
期刊：
影响因子：
4.8
通讯作者：
Ng, SC
中科院分区：
文献类型：
--
作者：
Chen, J;Wu, W;Ng, SC
Survivin 是凋亡蛋白抑制剂 (IAP) 家族的成员，可在大多数常见人类癌症中检测到，但在邻近的正常细胞中未检测到。先前的研究表明生存素与有丝分裂纺锤体相关并直接抑制半胱天冬酶活性。为了进一步研究生存素的功能，我们使用生存素反义（AS）寡核苷酸来下调正常细胞和癌细胞中生存素的表达。我们发现，抑制生存素表达会增加细胞凋亡和多倍体，同时减少软琼脂中的集落形成。免疫组织化学显示，没有survivin的细胞可以启动卵裂沟和收缩环，但不能完成胞质分裂，从而产生多核细胞。这些结果表明survivin在胞质分裂的后期以及细胞凋亡中发挥重要作用。
Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS) oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells, These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.