A novel and promising therapeutic approach for NSCLC: recombinant human arginase alone or combined with autophagy inhibitor.

摘要: Recombinant human arginase (rhArg), an enzyme capable of depleting arginine, has been shown to be effective therapeutic approach for various cancers. Non-small-cell lung cancer (NSCLC), a histological subtype pulmonary carcinoma, high rate morbidity and mortality in the world. Thus, need novel more treatment is urgent. In this study, it first time report that rhArg could induce significant cytotoxicity caspase-dependent apoptosis NSCLC cells. Subsequently, our research revealed dramatically stimulated autophagic response cells, which was proved by formation accumulation autophagosomes conversion microtubule-associated protein light chain 3 (LC3) from LC3-I LC3-II. Furthermore, blocking autophagy chloroquine or LY294002 remarkably enhanced rhArg-induced apoptosis, suggesting acted cytoprotective role rhArg-treated Further experiments showed two signaling pathways including Akt/mTOR extracellular signal-regulated kinase pathway, mitochondrial-derived reactive oxygen species (ROS) production were involved apoptosis. Meanwhile, N-acetyl-L-cysteine, common antioxidant, employed scavenge ROS, we detected significantly block cytotoxicity, indicating ROS played vital arginine degradation therapy. Besides, xenograft experiment combination with inhibitor potentiated anti-tumor efficacy vivo. Therefore, these results provided prospect viewpoint alone combined promising vivo vitro.