Decreased production of vascular endothelial growth factor in adriamycin-resistant breast cancer cells.
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-1alpha in the down-regulation of VEGF transcription in MCF-7/ADR cells. In addition, the basal activities of Akt and GSK-3beta 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.
Kim
Jung-Ae
JA
College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
Cho
Kyoung Bin
KB
Kim
Mi Ra
MR
Park
Byung Chul
BC
Kim
Sang Kyum
SK
Lee
Moo Yeol
MY
Kang
Keon Wook
KW
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D000903:Antibiotics, Antineoplastic; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin; D019869:Phosphatidylinositol 3-Kinases