P2-002 - The tumorigenic functions of NADPH oxidase 5 (NOX5) in oral tongue squamous cell carcinoma

Abstract

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common form of head and neck cancer. According to the data retrieved from Hong Kong Cancer Registry, there is a 48% increase in oral tongue cancer in our locality during the 10-year period (2001 -2010). We know that oral cancer has a remarkable increase in the intracellular reactive oxygen species (ROS) content. The oncogenic functions of ROS is well-documented. However, results from many trials had indicated that targeting cancer ROS as a mean for cancer treatment is not feasible. This is because high amount of antioxidant must be used to be effective. The effective dose is not tolerated by human body. In view of the crucial role of ROS, we attempted to identify the key ROS generating enzyme in oral cancer and test the feasibility of target treatment. Methods: Gene knock-down was performed with the use of shRNA-containing lentivector. In vitro proliferation assays and mouse xenograft models were used to validate the tumorigenic functions. QPCR and luciferase assays were employed to validate the downstream gene target. Results: Head and neck cancer has a differential upreglation of NADPH oxidase 5 (NOX5). NOX5 can generate superoxides without depending on any subunits. Thus, increasing NOX5 expression will have a direct impact on overall ROS generation in OTSCC. Knocking down NOX5 expression in OTSCC could lead to a remarkable reduce in the xenograft size. These data indicated that NOX5 is an important tumor gene in OTSCC with high potency in promoting OTSCC progression. Mechanistically, we showed that NOX5 is responsible for inducing hypoxia-inducible factor-1 (HIF-1). Also, we demonstrated that superoxide has a strong inducing effect on HIF-1 expression in OTSCC. Thus, the high expression of NOX5 might provide survival advantage to OTSCC at low oxygenation tumor microenvironment. Conclusions Our result provide a rationale for targeting NOX5 in OTSCC treatment.