Li Yuexia, Li Xiaohui, Liu Gang, Sun Rongqing, Wang Lirui, Wang Jing, Wang Hongmin
Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Department of Cardiovascular Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.
Biochem Biophys Res Commun. 2015 Jan 30;457(1):43-9. doi: 10.1016/j.bbrc.2014.12.080. Epub 2014 Dec 24.
The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P<0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P=0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression.
本研究旨在探讨TIPE2蛋白在人非小细胞肺癌(NSCLC)中的表达模式及其临床意义。我们通过免疫组织化学检测了96例NSCLC肿瘤样本中TIPE2的表达水平,然后分析其临床意义。此外,还在体外和体内实验性地检测了TIPE2对NSCLC细胞系H1299和A549生物学特性的作用。我们发现,与NSCLC组织相比,正常肺组织中TIPE2的表达水平显著更高(P<0.001),且TIPE2下调与晚期TNM分期显著相关(P=0.006)。肺癌细胞系中TIPE2的表达低于正常支气管细胞系HBE。在H1299和A549细胞中进行了TIPE2质粒转染。TIPE2过表达在体外抑制肺癌细胞增殖、集落形成和细胞侵袭,并在体内抑制肺肿瘤生长。此外,TIPE2转染降低了抗凋亡蛋白Bcl-XL和间充质标志物N-钙黏蛋白的表达。综上所述,我们的结果表明TIPE2可能在NSCLC进展中作为一种肿瘤抑制因子发挥作用。