Wang Shu Qian, Liu Yu, Yao Min Ya, Jin Jing
General Surgery Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
J Korean Med Sci. 2016 Oct;31(10):1586-94. doi: 10.3346/jkms.2016.31.10.1586.
Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.
在开发有效的治疗方法时,识别一种在胰腺肿瘤生长和转移中起关键作用的靶分子是必要的。该研究旨在探讨真核翻译起始因子3a(eIF3a)在胰腺癌细胞增殖和运动中的作用。我们的数据显示,与正常胰腺组织中的表达相比,eIF3a在胰腺导管腺癌中的表达上调。用特异性短发夹RNA(shRNA)敲低eIF3a导致胰腺癌SW1990和Capan-1细胞的细胞增殖和克隆形成能力显著降低。同样,异种移植小鼠中的胰腺癌细胞生长速率也受到损害。此外,伤口愈合试验表明,敲低eIF3a显著减缓了SW1990和Capan-1细胞中的伤口恢复过程。Transwell迁移和侵袭试验进一步表明,敲低SW1990和Capan-1细胞中的eIF3a可显著抑制细胞迁移和侵袭能力。对140例胰腺导管腺癌样本中eIF3a表达的统计分析显示,eIF3a表达与肿瘤转移和TNM分期显著相关。这些分析表明,eIF3a促进胰腺导管腺癌中的细胞增殖和运动。