Cellular retinol binding protein 1 transfection reduces proliferation and AKT-related gene expression in H460 non-small lung cancer cells

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 pur...

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Bibliographic Details
Published in:Molecular biology reports 2020-09, Vol.47 (9), p.6879-6886
Main Authors: Ferlosio, Amedeo, Doldo, Elena, Agostinelli, Sara, Costanza, Gaetana, Centofanti, Federica, Sidoni, Angelo, Orlandi, Augusto
Format: Article
Language:English
Subjects:
AKT protein
AKT1 protein
AKT2 protein
Animal Anatomy
Animal Biochemistry
Apoptosis
Biomedical and Life Sciences
Cancer therapies
Cell death
Cell differentiation
Cell proliferation
Down-regulation
FOXO1 protein
Gene expression
Histology
Life Sciences
Lung cancer
Morphology
Non-small cell lung carcinoma
Nuclear receptors
Original
Original Article
Retinoic acid
Retinoids
Small cell lung carcinoma
Stat3 protein
Transfection
Variance analysis
Vitamin A
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Summary: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 ( at RA) 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 at RA 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 at RA 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.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-020-05744-5