...
首页> 外文期刊>Oncogene >Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo
【24h】

Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo

机译:肿瘤细胞中细胞周期蛋白B1的稳定基因沉默增加了对紫杉醇的敏感性并导致体内生长停滞

获取原文
           

摘要

Cyclin B1 is the regulatory subunit of cyclin-dependent kinase 1 (Cdk1) and is critical for the initiation of mitosis. Accumulating data indicate that the deregulation of cyclin B1 is tightly linked to neoplastic transformation. To study the phenotype and the potential preclinical relevance, we generated HeLa cell lines stably transfected with the plasmids encompassing short hairpin RNA (shRNA) targeting cyclin B1. We demonstrate that the reduction of cyclin B1 caused inhibition of proliferation by arresting cells in G2 phase and by inducing apoptosis. Cells, entering mitosis, were impaired in chromosome condensation and alignment. Importantly, HeLa cells with reduced cyclin B1 were more susceptible to the treatment of small interfering RNA targeting Polo-like kinase 1 (Plk1) and to the administration of the chemotherapeutic agent taxol. Finally, HeLa cells with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to that of control cells. In summary, our data indicate that cyclin B1 is an essential molecule for tumor cell survival and aggressive proliferation, suggesting that the downregulation of cyclin B1, especially in combination with other molecular targets, might become an interesting strategy for antitumor intervention.
机译:细胞周期蛋白B1是细胞周期蛋白依赖性激酶1(Cdk1)的调节亚基,对于有丝分裂的启动至关重要。越来越多的数据表明,细胞周期蛋白B1的失调与肿瘤转化紧密相关。为了研究表型和潜在的临床前相关性,我们生成了稳定的HeLa细胞系,该细胞系被包含靶向细胞周期蛋白B1的短发夹RNA(shRNA)的质粒转染。我们证明,细胞周期蛋白B1的减少通过将细胞停滞在G2期并诱导凋亡来引起增殖抑制。进入有丝分裂的细胞的染色体浓缩和排列受到损害。重要的是,细胞周期蛋白B1降低的HeLa细胞更容易受到靶向Polo样激酶1(Plk1)的小干扰RNA的治疗和化疗紫杉醇的给药。最后,与对照细胞相比,细胞周期蛋白B1降低的HeLa细胞在裸鼠中显示出抑制的肿瘤生长。总之,我们的数据表明细胞周期蛋白B1是肿瘤细胞存活和侵袭性增殖的重要分子,这表明细胞周期蛋白B1的下调,尤其是与其他分子靶标的结合,可能成为抗肿瘤干预的有趣策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号