CYP1A1 and CYP1A2 expression levels are differentially regulated in three-dimensional spheroids of liver cancer cells compared to two-dimensional monolayer cultures.
Drug Metab Pharmacokinet
; 30(6): 434-40, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-26643992
ABSTRACT
Compared to two-dimensional (2D) monolayer cultures, three-dimensional (3D) tumor cell culture models are thought to be structurally more similar to the in vivo tumor microenvironment. We investigated the regulation of the expression of genes encoding the drug-metabolizing enzymes CYP1A1 and CYP1A2 in 3D spheroids comprised of cells of the human hepatocellular carcinoma cell JHH1, Huh7, and HepG2. Expression of CYP1A1 and CYP1A2 in the spheroids was higher than that in 2D cultured cells. Expression of CYP1A1 and CYP1A2 is regulated by aryl hydrocarbon receptor (AhR) in 2D cultured cells. Knockdown of AhR in spheroids suppressed CYP1A1 expression; however, CYP1A2 expression levels remained unchanged. Moreover, we found that pregnane X receptor (PXR) likely regulated CYP1A2 expression in JHH1, HepG2, and Huh7 spheroids and that CYP1A1 expression in JHH1 and Huh7 3D spheroids is regulated not only by AhR but also by PXR. It is well known that gene expression levels are different between 3D spheroids and 2D monolayer cultured cells, and our results indicate that the regulation of gene expression also varies between the two culture conditions. Taken together, these results underlie a novel finding regarding the regulation of drug-metabolizing enzyme expression in liver cancer cells growing as 3D spheroids.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Técnicas de Cultivo de Célula
/
Citocromo P-450 CYP1A1
/
Citocromo P-450 CYP1A2
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Drug Metab Pharmacokinet
Asunto de la revista:
FARMACOLOGIA
/
METABOLISMO
Año:
2015
Tipo del documento:
Article