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N-myc下游调控基因1的下调与胰腺癌增殖、侵袭和迁移增强有关。

Downregulation of the N-myc downstream regulated gene 1 is related to enhanced proliferation, invasion and migration of pancreatic cancer.

作者信息

Cen Gang, Zhang Kundong, Cao Jun, Qiu Zhengjun

机构信息

Department of General Surgery, Shanghai General Hospital of Nanjing Medical University, 100 Haining Road, Shanghai 200080, P.R. China.

出版信息

Oncol Rep. 2017 Feb;37(2):1189-1195. doi: 10.3892/or.2017.5355. Epub 2017 Jan 5.

DOI:10.3892/or.2017.5355
PMID:28075464
Abstract

The N-myc downstream regulated gene 1 (NDRG1) is differently expressed in human malignancies according to the tumor type. We investigated the expression of NDRG1 in pancreatic cancer tissues and cell lines as well as how it affects tumor growth, invasion and migration in pancreatic cancer cells. Experimental groups included NDRG1 overexpression and knockdown pancreatic cancer cell lines. Lentivirus-based empty vector transfected cells (NC group) were considered control groups. Proliferation, invasion and migration related proteins such as STAT3, MMPs, PTEN, PI3K/AKT were assessed by CCK-8, Transwell assay and western blotting. Efficient NDRG1 overexpression results in reduced cell proliferation, invasion and migration. Inversely, downregulation of NDRG1 promoted proliferation, invasion and migration. We also found NDRG1 could deactivate p-STAT3, PI3K, p-AKT, MMP2, MMP9 and activate PTEN. NDRG1 is a potential anti-oncogene. Its upregulation significantly decreases pancreatic cancer tumorigenesis, likely by inhibiting STAT3 and the PI3K/AKT signaling pathway.

摘要

N-myc下游调控基因1(NDRG1)在人类恶性肿瘤中的表达因肿瘤类型而异。我们研究了NDRG1在胰腺癌组织和细胞系中的表达,以及它如何影响胰腺癌细胞的肿瘤生长、侵袭和迁移。实验组包括NDRG1过表达和敲低的胰腺癌细胞系。基于慢病毒的空载体转染细胞(NC组)被视为对照组。通过CCK-8、Transwell实验和蛋白质印迹法评估增殖、侵袭和迁移相关蛋白,如STAT3、基质金属蛋白酶(MMPs)、PTEN、PI3K/AKT。有效的NDRG1过表达导致细胞增殖、侵袭和迁移减少。相反,NDRG1的下调促进了增殖、侵袭和迁移。我们还发现NDRG1可以使p-STAT3、PI3K、p-AKT、MMP2、MMP9失活,并激活PTEN。NDRG1是一种潜在的抑癌基因。其上调显著降低胰腺癌的肿瘤发生,可能是通过抑制STAT3和PI3K/AKT信号通路实现的。

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