Abstract
MCF-7/ADR cells, a doxorubicin-resistant human breast cancer cell line, have acquired resistance to several anti-cancer chemotherapeutic agents, such as anthracyclines and taxol. Here, we found that MCF-7/ADR cells produced lower levels of vascular endothelial growth factor (VEGF) than control MCF-7 cells. Molecular analyses using Western blots and reporter constructs containing either the human VEGF promoter or a minimal promoter for the transcription factor, hypoxia-inducible factor-1 (HIF-1), supported the involvement of HIF-1α in the down-regulation of VEGF transcription in MCF-7/ADR cells. In addition, the basal activities of Akt and GSK-3β were deregulated in MCF-7/ADR cells, and either the activation of PI3-kinase or the inhibition of GSK-3 restored the diminished transcription of VEGF. Chick chorioallantoic membrane (CAM) assay finally confirmed that angiogenesis intensity in MCF-7/ADR cells was significantly decreased compared with that in control MCF-7 cells.
Original language | English |
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Pages (from-to) | 225-232 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 268 |
Issue number | 2 |
DOIs | |
State | Published - 18 Sep 2008 |
Keywords
- Adriamycin-resistant breast cancer
- Angiogenesis
- HIF-1α
- VEGF