title: Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma.
abstract: Therapeutic doses of zoledronic acid markedly inhibit in vitro proliferation, chemotaxis, and capillarogenesis of bone marrow endothelial cells of patients with multiple myeloma. Zoledronic acid also induces a sizeable reduction of angiogenesis in the in vivo chorioallantoic membrane assay. These effects are partly sustained by gene and protein inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in an autocrine loop. Mevastatin, a specific inhibitor of the mevalonate pathway, reverts the zoledronic acid antiangiogenic effect, indicating that the drug halts this pathway. Our results provide evidence of a direct antiangiogenic activity of zoledronic acid on multiple myeloma patient-derived endothelial cells due to at least four different mechanisms identified either in vitro or in vivo. Tentatively, we suggest that the zoledronic acid antitumoral activity in multiple myeloma is also sustained by antiangiogenesis, which would partly account for its therapeutic efficacy in multiple myeloma.
authors: Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico, Piazza Giulio Cesare, 11, I-70124 Bari, Italy.
authors: Claudio
authors: C
authors: Scavelli
authors: Giulia
authors: G
authors: Di Pietro
authors: Teresa
authors: T
authors: Cirulli
authors: Mauro
authors: M
authors: Coluccia
authors: Angela
authors: A
authors: Boccarelli
authors: Teresa
authors: T
authors: Giannini
authors: Giuseppe
authors: G
authors: Mangialardi
authors: Raffaello
authors: R
authors: Bertieri
authors: Addolorata Maria Luce
authors: AM
authors: Coluccia
authors: Domenico
authors: D
authors: Ribatti
authors: Franco
authors: F
authors: Dammacco
authors: Angelo
authors: A
authors: Vacca
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004164:Diphosphonates / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D010641:Phenotype; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D000077211:Zoledronic Acid
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D004164:Diphosphonates; D007093:Imidazoles; D042461:Vascular Endothelial Growth Factor A; C012258:mevastatin; D000077211:Zoledronic Acid; D008148:Lovastatin; D040262:Receptors, Vascular Endothelial Growth Factor