In situ analysis of doxorubicin uptake and cytotoxicity in a 3D culture model of human HT-1080 fibrosarcoma cells.
Anticancer Res
; 26(6B): 4623-6, 2006.
Article
em En
| MEDLINE
| ID: mdl-17201187
ABSTRACT
In solid tumors, chemotherapeutics must adequately diffuse through the extracellular compartment to achieve their cytotoxic effect. Using quantitative microspectrofluorometry, both Doxorubicin penetration through three-dimensional (3D) collagen I matrices and its subsequent intranuclear accumulation into HT-1080 cells cultured in this microenvironment were directly assessed. Evidence that collagen delayed the Doxorubicin penetration for 1 h is presented. During that period, drug concentrations were lower in the nuclei in 3D compared to 2D matrices. Anthracyclines were also found to exhibit similar cytotoxicity in 2D and 3D after long term incubation. In conclusion, in this 3D culture model, collagen type I matrices delayed the early distribution of low molecular weight therapeutics and failed to affect their long-term cytotoxic effects, as previously reported. This model may provide a rationale for avoiding the emergence of intrinsic chemoresistance in tissue.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Fibrossarcoma
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article