Franks et al. BMC Res Notes (2016) 9:134 DOI 10.1186/s13104-016-1919-4 RESEARCH ARTICLE BMS-754807 is cytotoxic to non-small cell lung cancer cells and enhances the efects of platinum chemotherapeutics in the human lung cancer cell line A549 S. Elizabeth Franks, Robert A. Jones, Ritesh Briah, Payton Murray and Roger A. Moorehead * Abstract Background: Despite advances in targeted therapy for lung cancer, survival for patients remains poor and lung cancer remains the leading cause of cancer-related deaths worldwide. The type I insulin-like growth factor receptor (IGF-IR) has emerged as a potential target for lung cancer treatment, however, clinical trials to date have provided disappointing results. Further research is needed to identify if certain patients would beneft from IGF-IR targeted therapies and the ideal approach to incorporate IGF-IR targeted agents with current therapies. Methods: The dual IGF-IR/insulin receptor inhibitor, BMS-754807, was evaluated alone and in combination with platinum-based chemotherapeutics in two human non-small cell lung cancer (NSCLC) cell lines. Cell survival was determined using WST-1 assays and drug interaction was evaluated using Calcusyn software. Proliferation and apop- tosis were determined using immunofuorescence for phospho-histone H3 and cleaved caspase 3, respectively. Results: Treatment with BMS-754807 alone reduced cell survival and wound closure while enhancing apoptosis in both human lung cancer cell lines. These efects appear to be mediated through IGF-IR/IR signaling and, at least in part, through the PI3K/AKT pathway as administration of BMS-754807 to A549 or NCI-H358 cells signifcantly sup- pressed IGF-IR/IR and AKT phosphorylation. In addition of BMS-754807 enhanced the cytotoxic efects of carboplatin or cisplatin in a synergistic manner when given simultaneously to A549 cells. Conclusions: BMS-754807 may be an efective therapeutic agent for the treatment of NSCLC, particularly in lung cancer cells expressing high levels of IGF-IR. Keywords: BMS-754807, IGF-IR, Chemotherapy, Lung cancer, Proliferation, Apoptosis, Migration © 2016 Franks et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Background Lung cancer remains the leading cause of cancer-related deaths worldwide [1], and non-small cell lung cancer (NSCLC) represents ~80 % of the cases of lung cancer [2]. Lung cancer is often not diagnosed until later stages [3, 4] when it is no longer responsive to the standard treatment which is based on platinum chemotherapeutics and radiation [5–7]. Despite the development of a num- ber of new targeted therapies against epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and anaplastic lymphoma kinase (ALK), overall survival rates remain poor [7–10]. Tere is a need to develop new treatment strategies including new drugs and understand the most efective way to incorporate them into current treatments. Several type I insulin-like growth factor receptor (IGF-IR) targeting agents have been in clinical development, including monoclonal anti- bodies and tyrosine kinase inhibitors, which are reviewed by Scagliotti and Novello [11] and Chen and Sharon [12]. Figitumumab, a monoclonal antibody against IGF-IR, reached a phase III clinical trial in non-adenocarcinoma NSCLC that was ended due to poor outcomes [13]. Tis Open Access BMC Research Notes *Correspondence: rmoorehe@uoguelph.ca Department of Biomedical Science, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON N1G2W1, Canada