Polyamine transport inhibition with AMXT-1501 synergizes with cisplatin in HNSCC

Background: Head and neck squamous cell carcinoma (HNSCC) is a devastating disease that has generally poor prognosis. Cisplatin-based therapies remain the standard of care for these patients, however, many patients experience acute toxic effects develop resistance to treatment. Polyamine metabolism been shown promote growth cancer cells. AMXT-1501 compound in clinical trials inhibits polyamine transport, therefore we chose use combination cisplatin AMXT-1501. We sought investigate whether inhibition transport could synergize with HNSCC increase cytotoxicity. Methods: Cell proliferation was measured IC50 values were obtained syngeneic mouse head lines, MOC2, MEER PD-1 resistant, TAB2 cells after treatment Synergy determined by administering at ratio 1:10. used DCFDA assay measure relative ROS changes compared either alone. Flow cytometry using annexin V staining percentage undergoing apoptosis Finally, xenograft experiments performed C57 black mice test efficacy vivo. Results: The results synergistic effect on lines. increases production about 3-fold treatments also significantly apoptosis. vivo resulted 84% tumor resistant 90% MOC2 cells, which greater than individually. Conclusion: enhances cytotoxic vitro HNSCC. No conflict interest.