Abstract | BACKGROUND: 3D tumors express different adhesion receptors from those expressed in monolayers, leading to a distinct microenvironment. The third dimension also brings mass transport into relevance, as inadequate diffusion of oxygen produces hypoxia. This study investigates the effects of distinct 3D environments on hypoxia-associated apoptosis and drug resistance. MATERIALS AND METHODS: Under hypoxia and normoxia, U251 glioma cells and U87 astrocytoma cells were grown as spheroids on flat substrates, scaffolds seeded with dispersed cells, and spheroid-seeded scaffolds. The samples were subsequently treated with doxorubicin and resveratrol, known inducers of apoptosis. RESULTS: CONCLUSION: These findings suggest that in vitro, 3D models acquire greater apoptosis resistance via up-regulation of anti-apoptotic proteins, and that the precise mechanism depends on the individual 3D microenvironment.
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Authors | Jun W Kim, Won Jin Ho, Benjamin M Wu |
Journal | Anticancer research
(Anticancer Res)
Vol. 31
Issue 10
Pg. 3237-45
(Oct 2011)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 21965731
(Publication Type: Journal Article)
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Chemical References |
- BIRC5 protein, human
- Inhibitor of Apoptosis Proteins
- Proto-Oncogene Proteins c-bcl-2
- Survivin
- Vascular Endothelial Growth Factor A
- Fibroblast Growth Factor 2
- Doxorubicin
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Topics |
- Apoptosis
(drug effects)
- Cell Hypoxia
(drug effects)
- Cell Line, Tumor
- Down-Regulation
(drug effects)
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
(drug effects)
- Fibroblast Growth Factor 2
(metabolism)
- Humans
- Image Processing, Computer-Assisted
- Inhibitor of Apoptosis Proteins
(metabolism)
- Inhibitory Concentration 50
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Spheroids, Cellular
(pathology)
- Survivin
- Tissue Scaffolds
(chemistry)
- Tumor Microenvironment
(drug effects)
- Up-Regulation
(drug effects)
- Vascular Endothelial Growth Factor A
(metabolism)
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