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八聚体结合转录因子4(octamer-binding transcription factor 4,OCT4)是干细胞维持自我更新所必需的多潜能基因(pluripotent gene)。近年来已有多项临床研究报道,肺腺癌中存在OCT4阳性细胞的患者预后差,揭示OCT4是此类肿瘤的一个重要治疗靶标。该文借助小RNA(micro RNA)介导的基因沉默及cDNA表达芯片筛查技术,证明OCT4在肺腺癌细胞中具有转录调控功能。实验显示,15-脱氧–前列腺素J2(15d-PGJ2)与去铁胺(desferrioxamine,DFO)组合,可以显著下调肺腺癌细胞中OCT4的表达并有效抑制细胞增殖及集落形成。研究结果显示至少在体外实验条件下,药理性调控OCT4表达具有显著抗癌效应。该结果为探索肺癌靶向治疗新技术提供了思路。
Octoter-binding transcription factor 4 (OCT4) is a pluripotent gene necessary for stem cells to maintain self-renewal. In recent years, a number of clinical studies have reported that patients with OCT4-positive cells in lung adenocarcinomas have a poor prognosis, revealing that OCT4 is an important therapeutic target for such tumors. In this study, we demonstrated that OCT4 plays a transcriptional regulatory role in lung adenocarcinoma cells by means of microRNA-mediated gene silencing and cDNA microarray screening. Experiments show that combination of 15-deoxy-prostaglandin J2 (15d-PGJ2) and desferrioxamine (DFO) can significantly down-regulate OCT4 expression in lung adenocarcinoma cells and effectively inhibit cell proliferation and colony formation. The results show that at least in vitro experimental conditions, pharmacological regulation of OCT4 expression has a significant anti-cancer effect. The results provide a new idea for the exploration of targeted therapy of lung cancer.