title: Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells.
abstract: Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear.As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells treated with low doses of ZOL (10 μM). Microarrays analysis was used to identify, describe and summarize evidence regarding the molecular basis of actions of ZOL and of their possible direct anti-tumour effects. We validated gene expression results of specific transcripts involved in major cellular process by Real Time and Western Blot analysis and we observed inhibition of proliferation and migration through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Matrigel assay. We then focused on changes in the cytoskeletal components as fibronectin 1 (FN1), actin, and anti angiogenic compounds as transforming growth factor-β1 (TGF-β1) and thrombospondin 1 (THBS1). The up-regulation of these products may have an important role in inhibiting proliferation, invasion and angiogenesis mediated by ZOL.
authors.affiliation: Section of Medical Oncology, Department of Surgical and Oncology, University of Palermo, Palermo, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Insalaco
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Gaudio
authors.forename: Marianna
authors.initials: M
authors.lastname: Terrasi
authors.forename: Valeria
authors.initials: V
authors.lastname: Amodeo
authors.forename: Stefano
authors.initials: S
authors.lastname: Caruso
authors.forename: Lidia Rita
authors.initials: LR
authors.lastname: Corsini
authors.forename: Daniele
authors.initials: D
authors.lastname: Fanale
authors.forename: Naomi
authors.initials: N
authors.lastname: Margarese
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001862:Bone Resorption / Q000188:drug therapy; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D061986:MCF-7 Cells; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000077211:Zoledronic Acid
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004164:Diphosphonates; C067625:FN1 protein, human; D005353:Fibronectins; D007093:Imidazoles; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; D000077211:Zoledronic Acid