title: Decreased production of vascular endothelial growth factor in adriamycin-resistant breast cancer cells.
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-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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Kyoung Bin
authors.initials: KB
authors.lastname: Cho
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Kim
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Park
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.forename: Moo Yeol
authors.initials: MY
authors.lastname: Lee
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
mesh_terms: 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
chemical_list: 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