Title: The proteasome inhibitor Bortezomib induces head and neck cancer cells death in vitro and interferes with tumor growth of transplanted salivary gland cancer cells in mice

Abstract

Background: Head and neck cancer, the seventh most common cancer worldwide, has often an aggressive course with an emerging resistance to conventional chemotherapy. Therefore, the use of new therapeutic agents is being evaluated. Bortezomib is a proteasome inhibitor with potent in vitro and in vivo anticancer activities. Methods: in vitro antitumoral activity of Bortezomib was evaluated using human pharynx (FaDu), tongue (SCC-15, CAL-27), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) derived from an adenocarcinoma of the salivary gland from BALB-neuT male mice transgenic for the oncogene neu. We also analyzed the in vivo effects of Bortezomib in mice transplanted with murine SALTO-5 cells. Results: Bortezomib inhibited cells proliferation, induced apoptosis, modulated the expression and activation of molecules involved in pro-survival signal transduction pathways mediated by ErbB receptors (MAPK) and AKT, and inhibited proteasome activity in vitro. Furthermore, intraperitoneal administration of Bortezomib interfered with tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, prolonged their survival, modulated tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. Conclusions: Our findings suggest a potential use of Bortezomib for the treatment of head and neck carcinomas alone or in combination with conventional therapies or other biological drugs.

Biography

Dr. Monica Benvenuto received her PhD degree in Molecular Medicine at the University of Rome “Sapienza” in 2012. She was a research fellow at the University of Rome “Tor Vergata” for several years. Currently she is a researcher at “Saint Camillus International University of Health and Medical Sciences”, Rome. She is author of several publications in international journals of high scientific quality. Her main research activity is focused on the development of new experimental approaches for the treatment of tumors: cancer immunotherapy and study of the in vitro and in vivo effects of natural compounds, anticancer vaccines and intracellular signaling transduction pathways inhibitors on cancer cells growth.