Dipyridamole prevents triple-negative breast-cancer progression
| Autor: | Alessia Romano, Chiara Medaglia, Natascia Marino, Gennaro De Vita, Maria Nunzia Scoppettuolo, Daniela Spano, Massimo Zollo, Valeria Di Dato, Jean-Claude Marshall, Luigi Navas, Patricia S. Steeg, Daniela De Martino, Anna Maria Bello |
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| Přispěvatelé: | Spano, Daniela, Marshall, Jc, Marino, N, De Martino, D, Romano, Alessia, Scoppettuolo, Mn, Bello, Am, Di Dato, V, Navas, Luigi, De Vita, G, Medaglia, Chiara, Steeg, P, Zollo, Massimo |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Lung Neoplasms Phosphodiesterase Inhibitors Receptor ErbB-2 Apoptosis Metastasi Metastasis Immunoenzyme Techniques Mice Cell Movement Medicine NF-kB beta Catenin Triple-negative breast cancer Mitogen-Activated Protein Kinase 1 Mice Inbred BALB C Mitogen-Activated Protein Kinase 3 Reverse Transcriptase Polymerase Chain Reaction Cell Cycle NF-kappa B General Medicine Dipyridamole Flow Cytometry Primary tumor Receptors Estrogen Oncology Tumor microenvironment Immune cell infiltration Disease Progression Female Receptors Progesterone Signal Transduction medicine.drug medicine.medical_specialty ERK1/2-MAPK Blotting Western Mice Nude Breast Neoplasms Enzyme-Linked Immunosorbent Assay Real-Time Polymerase Chain Reaction Article Proinflammatory cytokine Wnt In vivo Cell Line Tumor Internal medicine Cell Adhesion Animals Humans RNA Messenger Cell Proliferation business.industry medicine.disease Xenograft Model Antitumor Assays Endocrinology Cancer research business |
| Zdroj: | Clinical & experimental metastasis 30 (2013): 47–68. doi:10.1007/s10585-012-9506-0 info:cnr-pdr/source/autori:Spano, Daniela; Marshall, Jean-Claude; Marino, Natascia; De Martino, Daniela; Romano, Alessia; Scoppettuolo, Maria Nunzia; Bello, Anna Maria; Di Dato, Valeria; Navas, Luigi; De Vita, Gennaro; Medaglia, Chiara; Steeg, Patricia S.; Zollo, Massimo/titolo:Dipyridamole prevents triple-negative breast-cancer progression/doi:10.1007%2Fs10585-012-9506-0/rivista:Clinical & experimental metastasis/anno:2013/pagina_da:47/pagina_a:68/intervallo_pagine:47–68/volume:30 Clin Exp Metastasis |
| Popis: | Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated beta-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkB alpha (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways. |
| Databáze: | OpenAIRE |
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