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Cellular retinol binding protein 1 transfection reduces proliferation and AKT-related gene expression in H460 non-small lung cancer cells.
Molecular Biology Reports ( IF 2.8 ) Pub Date : 2020-09-09 , DOI: 10.1007/s11033-020-05744-5
Amedeo Ferlosio 1 , Elena Doldo 1 , Sara Agostinelli 1 , Gaetana Costanza 1, 2 , Federica Centofanti 1 , Angelo Sidoni 3 , Augusto Orlandi 1, 4, 5
Affiliation  

In recent years, new treatments with novel action mechanisms have been explored for advanced non-small cell lung cancer (NSCLC). Retinoids promote cancer cell differentiation and death and their trafficking and action is mediated from specific cytoplasmic and nuclear receptors, respectively. The purpose of this study was to investigate the effect of Cellular retinol binding protein-1 (CRBP-1) transfection in H460 human NSCLC cell line, normally not expressing CRBP-1. H460 cells were transfected by using a vector pTargeT Mammalian expression system carrying the whole sequence of CRBP-1 gene. For proliferation and apoptosis studies, cells were treated with different concentrations of all-trans Retinoic Acid (atRA) and retinol. AKT-related gene expression was analyzed by using western blot and Signosis array and results analysed by one-way analysis of variance (ANOVA) or by t-student test. CRBP-1+ showed reduced proliferation and viability in basal condition and after atRA treatment when compared to empty-transfected H460 cells. Reduced proliferation in CRBP-1+ H460 cells associated to the down-regulation of pAKT/pERK/pEGFR-related genes. In particular, gene array documented the down-regulation of AKT and Stat-3-related genes, including M-Tor, Akt1, Akt2, Akt3, Foxo1, p27, Jun. Restoration of CRBP-1 expression in H460 cells reduced proliferation and viability in both basal condition and after atRA treatment, likely by down-regulating AKT-related gene level. Further studies are needed to better clarify how those CRBP-1-related intracellular pathways contribute to counteract NSCLC progression in order to suggest a potential tool to improve efficacy of retinoid anti lung cancer adjuvant therapy.



中文翻译:

细胞视黄醇结合蛋白1转染可降低H460非小肺癌细胞的增殖和AKT相关基因的表达。

近年来,已针对晚期非小细胞肺癌(NSCLC)探索了具有新颖作用机制的新疗法。类维生素A促进癌细胞的分化和死亡,它们的运输和作用分别由特定的细胞质和核受体介导。这项研究的目的是研究细胞视黄醇结合蛋白1(CRBP-1)转染对通常不表达CRBP-1的H460人NSCLC细胞系的影响。通过使用携带CRBP-1基因的整个序列的载体pTargeT哺乳动物表达系统转染H460细胞。对于增殖和凋亡的研究,细胞用不同浓度的治疗全反式维甲酸(RA)和视黄醇。使用蛋白质印迹和Signosis阵列分析与AKT相关的基因表达,并通过单向方差分析(ANOVA)或t检验来分析结果。CRBP-1 +显示出降低的增殖和生存力在基础条件下和后相比空转染的H460细胞中时RA治疗。与pAKT / pERK / pEGFR相关基因的下调相关的CRBP-1 + H460细胞增殖减少。特别是,基因阵列证明了AKT和Stat-3相关基因的下调,包括M-Tor,Akt1,Akt2,Akt3,Foxo1,p27,Jun。H460细胞中CRBP-1表达的还原降低了增殖和生存能力。在这两个基础条件,之后RA治疗,可能是通过下调AKT相关基因水平来实现的。需要进一步的研究来更好地阐明那些与CRBP-1相关的细胞内途径如何抵消NSCLC进程,从而为改善类维生素A抗肺癌辅助疗法的疗效提供潜在的工具。

更新日期:2020-09-10
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