The effect of Arginase on Small Cell Lung Cancer

Introduction: Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases. SCLC is characterized by easy to relapse, and current treatment lacks tumor specificity. BCT-100 is a pegylated arginase which shows anticancer activity in human melanoma, hepatocellular carcinoma and acute myeloid leukemia. One of resistance mechanisms is overexpression of argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC). The aim of this study is to determine the effect of BCT-100 on SCLC. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability of different SCLC cell lines after BCT-100 treatment. Western blotting was employed to evaluate the protein expression. Knockdown of OTC was performed using specific siRNA. Result: After incubation of BCT-100 for 72 hours, the IC50 values of H69, DMS79, H187, H209, H526, H841 and SW1271 cells were 462.9 ± 112.2, >1000, 24.9 ± 6.4, 8.6 ± 0.8, 10.1 ± 0.7, >1000 and 49.2 ± 7.4 mU/mL respectively. Overexpression of ASS1 in H69 and DMS79 cells and OTC in H841 cells might account for the resistance to BCT-100. Furthermore, knockdown of OTC increased sensitivity of BCT-100 in H841 cells partially via apoptosis. Moreover, co-incubation of N-acetylcysteine (NAC, an antioxidant) with BCT-100 reversed BCT-100-induced cell death via inhibition of apoptosis in H526 cells. Conclusion: The SCLC cell lines with low expression of ASS and OTC were responsive to BCT-100 treatment partially via ROS-induced apoptosis. BCT-100 showed potential anticancer activity in lung cancer research. Acknowledgment: None to declare