Recombinant human arginase induces apoptosis through oxidative stress and cell cycle arrest in small cell lung cancer.

摘要: Small cell lung cancer (SCLC) accounts for approximately 13% of all cases. is characterized by frequent relapse, and current treatments lack tumor specificity. Arginine a non-essential amino acid human normal cells but critical to some that cannot synthesize arginine. Therefore, arginine deprivation has become potential therapeutic option selected tumors. BCT-100 pegylated arginase documented anticancer activity in auxotrophic tumors, such as melanoma, hepatocellular carcinoma, acute myeloid leukemia. One the resistance mechanisms treatment overexpression argininosuccinate synthetase (ASS1) ornithine transcarbamylase (OTC), two important enzymes urea cycle. We 9 SCLC 1 non-small carcinoma lines determine growth inhibition effects established with low expression ASS1 OTC are relatively sensitive treatment. Knocking down H841 line could potentiate its sensitivity concentration was sharply decreased, accompanied apoptosis through oxidative stress well G1 cycle arrest. In addition, showed an effect on H446 H510A xenograft models lowering levels inducing apoptosis.