Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells
Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells
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DOI：
10.1038/emm.2006.28
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发表时间：
2006-06-30
影响因子：
12.8
通讯作者：
Liu, Guo-Liang
中科院分区：
文献类型：
--
作者：
Du, Zhen-Xian;Zhang, Hai-Yan;Liu, Guo-Liang
Suvivin是凋亡抑制蛋白（inhibitor of apoptosis protein，IAP）家族的新成员，在多种肿瘤中过度表达，并与肿瘤的生物学侵袭性相关。本研究的目的是研究生存素在人甲状腺髓样癌（IVITC）和MTC细胞株TT中的表达，探讨生存素表达与IVITC临床病理特征的关系，以及抗生存素寡核苷酸（ASODNs）对TT细胞生长和凋亡的影响。采用免疫组织化学方法检测10例正常甲状腺（NT）和10例MTC组织石蜡包埋标本及TT细胞中Survivin的表达。在TT细胞中，我们通过RT-PCR和Western blot分析证实了Survivin的表达及其被ASODNs下调，并通过MTT法和凋亡分析（包括DNA梯状电泳、吖啶橙子/溴化乙锭染色和流式细胞仪细胞周期分析）研究了ASODNs对TT细胞存活和生长的影响。免疫组织化学分析显示，MTC和TT细胞中的高表达，而NT中没有免疫反应性。统计学分析显示Survivin的表达与MTC的临床病理特征无明显相关性。在TT细胞中，Survivin在mRNA和蛋白水平上的表达被证实，并且可以被ASODNs下调，伴随着生存力和生长的下降，以及凋亡的增加。我们的研究结果表明，Survivin在MTC中发挥重要作用，不依赖于传统的临床病理因素，ASODNs是一种很有前途的以Survivin为靶点的基因治疗MTC的方法。
Suvivin is a novel member of the inhibitor of apoptosis protein (IAP) family, which is known to be over-expressed in various carcinomas and associated with their biologically aggressive characteristics. The aim of this study was to investigate survivin expression in human medullary thyroid carcinoma (IVITC) and a MTC cell line TT, correlate suvivin expression with clinicopathologic features of IVITC, and test effects of antisurvivin oligonucleotides (ASODNs) on growth and apoptosis of TT cells. Survivin expression was immunohistochemically determined in formalin-fixed and paraffin-embedded specimens obtained from 10 cases of normal thyroid (NT) and 10 cases of MTC, and in TT cells. In TT cells, we confirmed survivin expression and its down-regulation by ASODNs using RT-PCR and Western blot analyses, and investigated effects of ASODNs on viability and growth by MTT assay and apoptosis by apoptotic analyses including DNA laddering assay, acridine orange/ethidium bromide staining and flow cytometric cell cycle analysis. Immunohistochemical analysis showed high survivin expression in MTC and TT cells, whereas no immunoreactivity was detectable in NT. Statistical analyses revealed no significant correlation of survivin expression with the clinicopathologic features of MTC. In TT cells, survivin expression at both mRNA and protein levels was confirmed and could be down-regulated by ASODNs concomitant with decrease in viability and growth, and increase in apoptosis. Our results suggest that survivin plays an important role in MTC independent of the conventional clinicopathologic factors, and ASODNs is a promising survivin- targeted gene therapy for MTC.