Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells.
Bottom Line: 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.
Affiliation: Section of Medical Oncology, Department of Surgical and Oncology, University of Palermo, Palermo, Italy.Show MeSH
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Mentions: To identify the lower dose of ZOL sufficient to induce an anti-proliferative effect on MCF-7 cell proliferation, we tested different concentrations (10–100 μM) of ZOL for 24, 48 or 72 hrs.Cell count showed that cell growth was inhibited by ZOL versus control at all concentrations used (Fig. 1). In particular, tumour cell growth was reduced to about 40% at a ZOL concentration of 100 μM over a period of incubation of 24 hrs whereas the lower ZOL concentration (10 μM) was slightly less efficient (20%), but effective. Consider that inhibition rates of 10 and 100 μM of ZOL were not shown a significant difference, we can assert that the treatment at lower concentration for only 24 hrs is sufficient to induce an inhibition of proliferation, also confirmed by determination of number of metabolically active cells by MTT assay (Fig. 1A and B). On the basis of these data, we have selected this concentration of ZOL for all the subsequent experiments.
Affiliation: Section of Medical Oncology, Department of Surgical and Oncology, University of Palermo, Palermo, Italy.