BMS-754807 is cytotoxic to non-small cell lung cancer cells and enhances the effects of platinum chemotherapeutics in the human lung cancer cell line A549. (December 2016)

• Record Type: Journal Article
• Authors: Franks, S.; Jones, Robert; Briah, Ritesh; Murray, Payton; Moorehead, Roger
• Is Part Of: BMC research notes. Volume 9:Number 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: BMS-754807 -- IGF-IR -- Chemotherapy -- Lung cancer -- Proliferation -- Apoptosis -- Migration; Medicine -- Periodicals; Biology -- Periodicals; 610.5
• DOI: 10.1186/s13104-016-1919-4
• Languages: English
• ISSNs: 1756-0500

Abstract

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 benefit 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 apoptosis were determined using immunofluorescence 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 effects 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 significantly suppressed IGF-IR/IR and AKT phosphorylation. In addition of BMS-754807 enhanced the cytotoxic effects of carboplatin or cisplatin in a synergistic manner when given simultaneously to A549 cells. Conclusions BMS-754807 may be an effective therapeutic agent for the treatment of NSCLC, particularly in lung cancer cells expressing high levels of IGF-IR.