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敲低 Oct4 和 Nanog 的表达抑制了胰腺癌细胞的干性。

Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells.

机构信息

Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, PR China; Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, PR China; Visitor Scholar of Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.

出版信息

Cancer Lett. 2013 Oct 28;340(1):113-23. doi: 10.1016/j.canlet.2013.07.009. Epub 2013 Jul 17.

Abstract

Pancreatic cancer is notorious for its difficult diagnosis at early stage and poor recurrence-free prognosis. This study aimed to investigate the possible involvement of Oct4 and Nanog in pancreatic cancer. The high expressions of Oct4 and Nanog in human pancreatic cancer tissues were found to indicate a worse prognostic value of patients. The pancreatic cancer stem cells (PCSCs) that isolated from PANC-1 cell line by flow cytometry exhibited high expressions of Oct4 and Nanog. To investigate whether Oct4 and Nanog play crucial role in maintaining the stemness of PCSCs, double knockdown of Oct4 and Nanog demonstrated that Oct4 and Nanog significantly reduced proliferation, migration, invasion, chemoresistance, and tumorigenesis of PCSCs in vitro and in vivo. The altered expression of the genes related to pancreatic carcinogenesis, metastasis, drug resistance and epithelial-mesenchymal transdifferentiation (EMT) might affect the biological characteristics of PCSCs. Our results suggest that Oct4 and Nanog may serve as a potential marker of prognosis and a novel target of therapy for pancreatic cancer.

摘要

胰腺癌以其早期诊断困难和复发预后不良而臭名昭著。本研究旨在探讨 Oct4 和 Nanog 是否参与胰腺癌。发现人胰腺癌组织中 Oct4 和 Nanog 的高表达表明患者的预后价值更差。通过流式细胞术从 PANC-1 细胞系中分离出的胰腺癌干细胞(PCSCs)表现出 Oct4 和 Nanog 的高表达。为了研究 Oct4 和 Nanog 是否在维持 PCSCs 的干性中起关键作用,Oct4 和 Nanog 的双重敲低表明,Oct4 和 Nanog 显著降低了 PCSCs 的体外和体内增殖、迁移、侵袭、化疗耐药性和致瘤性。与胰腺发生、转移、耐药和上皮-间充质转化(EMT)相关的基因表达的改变可能会影响 PCSCs 的生物学特性。我们的研究结果表明,Oct4 和 Nanog 可能作为胰腺癌预后的潜在标志物和治疗的新靶点。

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