Open AccessAnalysis of molecular mechanisms and anti‐tumoural effects of zoledronic acid in breast cancer cells
Author(s) -
Insalaco Lavinia,
Gaudio Francesca Di,
Terrasi Marianna,
Amodeo Valeria,
Caruso Stefano,
Corsini Lidia Rita,
Fanale Daniele,
Margarese Naomi,
Santini Daniele,
Bazan Viviana,
Russo Antonio
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01527.x
Subject(s) - zoledronic acid , breast cancer , cancer research , angiogenesis , bone resorption , bisphosphonate , cancer , medicine , biology , chemistry , osteoporosis
Zoledronic acid ( ZOL ) is the most potent nitrogen‐containing bisphosphonate ( N ‐ BP s) 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 .