The expression and role of NADPH Oxidase 2 in colon cancer

Abstract

Background Nicotinamide adenine dinucleotide phosphate (NADPH) Oxidases (NOXs) are transmembrane proteins that generate reactive oxygen species. Recent studies have reported that NOXs play important roles in the progression of various cancers. However, the expression and role of NOX2 in colon cancer is unclear. Therefore, this study aimed to investigate the expression of NOX2 and effects on the prognosis of patients with colon cancer, and also examined the pathophysiological role of NOX2 in cell proliferation and motility. Methods We used 116 primary colon cancer samples obtained from patients who underwent curative resection for stage II or III colon cancer for immunohistochemistry to assess the relationship between NOX2 expression and clinicopathological factors and evaluate the prognostic significance of NOX2 expression in colon cancer patients. The expression levels of NOX2 protein and mRNA in human colon cancer cell lines were analyzed and two highly NOX2 expressed cell lines (HCT116 and RKO) were used for further study. Knockdown experiments with NOX2 siRNA were performed, and the effects on cell proliferation, cell cycle progression, migration, and invasion were analyzed. Results Immunohistochemical staining revealed that NOX2 protein was scarcely expressed in noncancerous tissue compared to cancer tissue, and 45 samples (38.8%) had positive staining for NOX2 expression in cancer tissue. No clinicopathological factor was significantly associated with NOX2 expression. The 5-year recurrence-free survival rate of the NOX2 positive group was significantly lower than that of the NOX2 negative group (61.1% vs. 79.3%, p = 0.029). NOX2 depletion using siRNA significantly inhibited cell proliferation, G1 to S phase cell cycle progression, migration, and invasion in the two cell lines. Conclusions NOX2 expression affects the prognosis of colon cancer patients, as well as the tumorigenesis of colon cancer cells. NOX2 may be a novel biomarker and therapeutic target for colon cancer patients.