Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer
| Autor: | Davide Melisi, Sabino De Placido, A. Raffaele Bianco, Giampaolo Tortora, Fortunato Ciardiello, Rosa Caputo, Bianca Maria Veneziani, Vincenzo Damiano, Roberto Bianco |
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| Přispěvatelé: | Melisi, Davide, Caputo, R, Damiano, Vincenzo, Bianco, Roberto, Veneziani, BIANCA MARIA, Bianco, Ar, DE PLACIDO, Sabino, Ciardiello, F, Tortora, Giampaolo |
| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Endocrinology Diabetes and Metabolism EGFR Mice Nude Apoptosis Breast Neoplasms Pharmacology Zoledronic Acid Prostate cancer Mice Endocrinology Gefitinib In vivo Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Epidermal growth factor receptor Sulfonamides biology Cyclooxygenase 2 Inhibitors Diphosphonates business.industry Imidazoles Prostatic Neoplasms Proteins Cell cycle COX-2 medicine.disease Xenograft Model Antitumor Assays Zoledronic acid Oncology Mechanism of action Cancer cell biology.protein Quinazolines Pyrazoles Female medicine.symptom business medicine.drug Signal Transduction |
| Zdroj: | Endocrine-related cancer. 12(4) |
| ISSN: | 1351-0088 |
| Popis: | Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting. |
| Databáze: | OpenAIRE |
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