Effects of repurposed drug candidates nitroxoline and nelfinavir as single agents or in combination with erlotinib in pancreatic cancer cells

• DOI: 10.1186/s13046-018-0904-2
• Publication Date: 2018-09-21T15:23:15Z
• Authors: Serena Veschi; Laura De Lellis; Rosalba Florio; Paola Lanuti; Alberto Massucci; Nicola Tinari; Michele De Tursi; Pierluigi di Seba...; Marco Marchisio; Clara Natoli; Alessandro Cama
• Keywords: Nelfinavir; Viability assay; Clonogenic assay; MTT assay; Erlotinib Hydrochloride

Pancreatic cancer (PC) is the fourth most common cause of death. Combination therapies with classical chemotherapeutic agents improved treatment advanced PC at cost a relevant toxicity, but 5-year survival rate remains below 5%. Consequently, new therapeutic options for this disease are urgently needed. In study, we explored effect two repurposed drug candidates nelfinavir and nitroxoline, approved non-anticancer human use, in cell lines. Nelfinavir nitroxoline were tested as single agents, or combinations without erlotinib, targeted treatment.The effects drugs on viability AsPC-1, Capan-2 BxPC-3 lines assessed by MTT. The impact treatments cycle distribution apoptosis was analyzed flow cytometry. proteins regulation evaluated western blot. Self-renewal capacity after using clonogenic assay.When used decreased viability, affected reduced expression proteins. variable among Moreover, these drastically impaired activity three Combinations resulted dose- cell-dependent synergistic viability. These paralleled alterations more consistent induction compared to agents. Treatments induced drastic impairment lines.This study shows that non-antitumor drugs, combination have antitumor appear comparable, some case pronounced than those erlotinib Our results support repurposing treatment.