Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and induction of apoptosis in human esophageal cancer cells
Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and induction of apoptosis in human esophageal cancer cells
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通过 siRNA 沉默 Polo 样激酶 (Plk) 1 可抑制人食管癌细胞生长并诱导细胞凋亡
DOI：
10.1159/000151367
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Song, Fangzhou
中科院分区：
文献类型：
--
作者：
Bu, Youquan;Yang, Zhengmei;Song, Fangzhou
食管癌是世界上最常见的癌症死亡原因之一。 Polo 样激酶 1 (Plk1) 在人类肿瘤中过度表达，对包括食道癌在内的许多癌症具有预后价值，表明其作为治疗靶点的潜力。在这项研究中，我们利用小干扰 RNA (siRNA) 进行 RNA 沉默技术，研究了 Plk1 在食管癌中的治疗潜力。针对 Plk1 的合成 siRNA 双链体被引入 4 个食管癌细胞系中，随后导致细胞中 Plk1 表达的显着抑制。我们发现，Plk1 的靶向缺失导致了严重的有丝分裂灾难（有丝分裂细胞周期停滞以及一些有丝分裂事件的缺陷，例如姐妹染色单体的不完全分离和胞质分裂的失败），随后导致大量细胞凋亡，并最终导致所研究的所有 4 种食管癌细胞系的生长和活力显着下降。此外，我们的结果还表明，Plk1 耗竭诱导的有丝分裂停滞是由 cdc2/cyclin B1 复合物失活介导的。综上所述，我们的研究强烈表明 Plk1 可能作为人类食管癌的潜在治疗靶点。版权所有 (c) 2008 S. Karger AG，巴塞尔。
Esophageal cancer ranks among one of the most frequent causes of cancer death in the world. Polo-like kinase 1 (Plk1) is overexpressed in human tumors and has prognostic value in many cancers including esophageal cancer, indicating its potential as a therapeutic target. In this study, we investigated the therapeutic potential of Plk1 in esophageal cancer using the technique of RNA silencing via small interfering RNA ( siRNA). Synthetic siRNA duplexes against Plk1 were introduced into 4 esophageal cancer cell lines, which subsequently resulted in a significant inhibition in Plk1 expression in the cells. We found that the targeted depletion of Plk1 caused a dramatic mitotic catastrophe ( mitotic cell cycle arrest as well as defects in several mitotic events such as incomplete separation of sister chromatids and failure of cytokinesis) followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth and viability of all 4 esophageal cancer cell lines studied. In addition, our results also indicated that the mitotic arrest induced by Plk1 depletion is mediated by the inactivation of the cdc2/cyclin B1 complex. Taken together, our study strongly suggests that Plk1 may serve as a potential therapeutic target in human esophageal cancer. Copyright (c) 2008 S. Karger AG, Basel.