The effects of NOX2 and NOX4 inhibitors on panc-1 cell viability

Abstract: Pancreatic cancer is a leading cause of cancer related deaths worldwide and has a low survival rate 1 year after diagnosis. It is therfore important to identify new biomarkers and treatments to improve disease outcome. This experiment investigated the effects of different NOX2 and NOX4 inhibitors on Panc-1 cell lines. Following 48 hours treatment, Cell viability analysis, Caspase 3/7 as well as ROS levels where measured to see how these factors were affected by the treatments. As the PI3K/AKT/mTOR and MAPK/ERK pathways, as well as G6PD and VEGF have been shown to influence cancer metastasis and invasiveness, a gene expression analysis (VEGF, G6PD, AKT2, ERK2) was also conducted. Results obtained showed a general decrease in cell viability with increasing concentrations of inhibitors used. While a general increase in Caspase 3/7 activity was observed, M166-0.6μM treatment showed decreased Caspase 3/7 activity, suggesting that other non-apoptotic cell death pathways such as necrosis could have been at play. A general increase in ROS activity was also observed and unexpected. Gene expression showed an increase in G6PD activity which could mean, the cancer cells increased antioxidant system activity to achieve redox balance due to the increased ROS levels. Some results obtained where unexpected and make it difficult to conclude how the treatments decreased cell viability. The results also suggest that other currently unknown mechanisms were at play in influencing cell viability. Most importantly, the results show that completely inhibiting NOX2 and NOX4 lead to the most significant decrease in cell viability.