Dong Zhizhen, Chen Jianrong, Yang Xuli, Zheng Wenjie, Wang Li, Fang Miao, Wu Mengna, Yao Min, Yao Dengfu
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
Department of Respiratory Medicine, Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
Oncotarget. 2018 Jan 9;9(16):12705-12717. doi: 10.18632/oncotarget.24061. eCollection 2018 Feb 27.
Lung cancer is the most common malignant tumor with increasing angiopoietin-2 (Ang-2) and a high rate of metastasis. However, the mechanism of Ang-2 enhancing tumor proliferation and facilitating metastasis remains to be clarified. In this study, Ang-2 expression and its gene transcription on effects of biological behaviors and epithelial-mesenchymal transition (EMT) were investigated in lung cancers. Total incidence of Ang-2 expression in the cancerous tissues was up to 91.8 % (112 of 122) with significantly higher (χ=103.753, =7.883, =0.005), differentiation degree (χ=4.554, =0.033), tumor node metastasis (TNM) staging (χ=5.039, =0.025), and 5-year survival rate (χ =11.220, =18.881, =0.81, =0.776) or III & IV (χ=1.845, =0.174). Over-expression of Ang-2 or Ang-2 mRNA in lung A549 and NCI-H1975 cells were identified among different cell lines. When silencing in A549 cells with specific shRNA-1 transfection, the cell proliferation was significantly inhibited in a time-dependent manner, with up-regulating E-cadherin, down-regulating Vimentin, Twist, and Snail expression, and decreasing invasion and metastasis of cancer cell abilities, suggesting that promote tumor metastasis through increasing EMT, and it could be a potential target for lung cancer therapy.
肺癌是最常见的恶性肿瘤,血管生成素-2(Ang-2)水平升高且转移率高。然而,Ang-2促进肿瘤增殖和转移的机制仍有待阐明。本研究在肺癌中研究了Ang-2表达及其基因转录对生物学行为和上皮-间质转化(EMT)的影响。癌组织中Ang-2表达的总发生率高达91.8%(122例中的112例),在分化程度(χ=4.554,P=0.033)、肿瘤淋巴结转移(TNM)分期(χ=5.039,P=0.025)以及5年生存率(χ=11.220,P=18.881,df=0.81,P=0.776)或III和IV期(χ=1.845,P=0.174)方面显著更高。在不同细胞系中鉴定出肺癌A549和NCI-H1975细胞中Ang-2或Ang-2 mRNA的过表达。当用特异性shRNA-1转染沉默A549细胞中的Ang-2时,细胞增殖以时间依赖性方式显著受到抑制,同时E-钙黏蛋白上调,波形蛋白、Twist和Snail表达下调,癌细胞侵袭和转移能力降低,表明Ang-2通过增加EMT促进肿瘤转移,它可能是肺癌治疗的一个潜在靶点。