P3-14-6SYNERGISTIC CYTOTOXIC EFFECT OF THE COMBINATION OF AMRUBICIN AND ERLOTINIB IN NSCLC WITHOUT EGFR MUTATION

Abstract Background: Standard second-line chemotherapy against advanced non-small-cell lung cancer (NSCLC) is a single agent such as docetaxel, pemetrexed, or erlotinib (Erl). We recently reported that the combination of amrubicin (AMR) and Erl was clinically safe and effective for pre-treated advanced NSCLC patients. The aim of this research is to confirm the experimental effectiveness of the combination and to investigate mechanism of the action. Methods: We perform the growth inhibition assay for NSCLC cell lines and make two-dimension isobolograms to estimate the synergy of the combination. Flowcytemetry analysis (FACS) and Western blot analysis (WB) is also done in vitro. In vivo growth inhibition assay using subcutaneous model on SCID mice is performed. Results: The combination of AMR and E had significant synergistic effect on EGFR wild type NSCLC cell line A549, while additive effect on EGFR mutant cell line PC-9. Sub G0-G1 population on FACS was significantly increased in A549 cells treated with combination. The combination therapy activated apoptosis related proteins in WB and showed strong growth inhibition of subcutaneous tumors on SCID mice. Conclusion: The combination of AMR and E synergistically induced apoptosis and growth inhibition on A549 cells. This combination may be a promising therapeutic option against advanced NSCLC without EGFR mutation.