Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21.

Abstract

The objective of this study was to detect the effect of NADPH oxidase (NOX) inhibition on metastasis of lung cancer. Primary human lung cancer cells were isolated from surgical tissues using the Cancer Cell Isolation Kit. Invasion was detected using the BD Biocoat Matrigel Invasion Chamber assay. Expressions of microRNA-21 (miR-21), PTEN, MMP9, and p47 were detected by qPCR. Groups of nude mice were challenged with A549 cells with or without DPI and detected for tumor metastasis and survival. NOX inhibition in human lung cancer cells significantly reduced their invasive potential in vitro. NOX inhibition in vivo led to decreased metastasis of human lung cancer and prolonged the survival time of tumor-bearing nude mice. Further, NOX inhibition resulted in decreased expression of miR-21 in human lung cancer cells. Increased expression of miR-21 abrogated the effect of NOX inhibitor on metastasis of human lung cancer in vitro and in vivo. Decreased expression of miR-21 facilitated the effect of NOX inhibitor on metastasis of human lung cancer in vitro and in vivo. Furthermore, increased expression of PTEN and decreased expression of MMP9 were observed in human lung cancer cells in response to NOX inhibition. Finally, close correlations of miR-21 expression levels with NADPH oxidase expression level and differentiation state of tumor cells were observed in lung cancer patients. Inhibition of NADPH oxidase protected against metastasis of human lung cancer cells by decreasing miR-21 expression, which could facilitate the understanding of lung cancer pathogenesis and provided clues for the development of novel therapeutics for lung cancer patients.