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: We found that treatment with ZOL induces transcription and protein expression of some matrix and cytoskeletal components, such as Fibronectin and actin, involved in cancer microenvironment. In particular, the up-regulation of gene coding for FN1 shown by microarray (fold change of 1.93) was confirmed by Real Time RT-PCR with a fold change of 2.3 compare with control (Fig. 4A) and mRNA expression of actin, analysed by Real time RT-PCR, showed a fold change of 1.5. Interestingly, a high protein expression is maintained even at longer treatment (at 96 hrs), and with the most activating effect in the protein products, indicating the potential consequences of ZOL treatment on the morphology and cell motility, considered the cellular roles of FN1 and actin as factors that can change the ECM (Fig. 4B).
Affiliation: Section of Medical Oncology, Department of Surgical and Oncology, University of Palermo, Palermo, Italy.