445 NQO1 suppresses the growth of cutaneous squamous cell carcinoma cells

Abstract

Cutaneous squamous cell carcinoma (SCC) is an easily occurred cancer, which can worsen the quality of life considerably. It is known that external stimulus such as ultraviolet (UV) radiation induces cutaneous SCC via provoking oxidative stress. NAD(P)H dehydrogenase 1 (NQO1) is a ubiquitous flavoenzyme that functions as a guardian against oxidative stress. However, the effect of NQO1 on cutaneous SCC is not clearly elucidated. In this study, we investigated the effect of NQO1 on cutaneous SCC cells using the recombinant adenoviruses that can upregulate and/or downregulate NQO1 expression. Overexpression of NQO1 resulted in significant decrease of cell proliferation and colony forming activity of SCC lines (SCC12 and SCC13 cells). By contrast, knockdown of NQO1 increased the cell proliferation and colony forming activity. Accordingly, the levels of proliferation-related regulators, such as CDK4, CDK6, SOX2 and p63, were decreased by overexpression of NQO1, while those were increased by knockdown of NQO1. In addition, NQO1 affected the invasion and migration of SCC cells in a very similar way, with the regulation of epithelial-mesenchymal transition (EMT)-related molecules, including E-cadherin, N-cadherin, Vimentin, Snail and Slug. Finally, overexpression of NQO1 decreased the level of phosphorylated AKT, JNK and p38 MAPK, while knockdown of NQO1 increased the level of phosphorylated signaling molecules. Based on these data, NQO1 has tumor suppressive function in cutaneous SCC cells.