Inhibition of ornithine decarboxylase facilitates pegylated arginase treatment in lung adenocarcinoma xenograft models

INTRODUCTION: Arginine depletion has shown anticancer effects among arginine auxotrophic cancers. Pegylated arginase (BCT-100) depletes arginine by converting arginine to ornithine. In this study, BCT-100 inhibited cell growth in a panel of lung adenocarcinoma cell lines while stimulated tumor growth in most lung adenocarcinoma xenograft models. Furthermore, ornithine decarboxylase (ODC) was induced by BCT-100 in two solid xenograft models with tumor growth stimulating effect. We postulate that accumulated ornithine was used to produce polyamines by ODC which promoted tumor growth. And ODC inhibition might rescue the therapeutic effect of BCT-100 treatment in lung adenocarcinoma ...published_or_final_versio