Overexpression of IκBα suppresses lung cancer growth through reduced VEGF production

Objective. In this experiment, we investigated the effects of overexpressed IκBα on human lung cancer cell line H460 proliferation in vitro and in vivo. Methods. The IκBα gene was transferred by recombinant adenovirus, AdIκBα. Cell growth suppression was evaluated by MTS assay in vitro and tumor growth suppression was evaluated by direct measurement of tumor size established on nude mice. Results. The results suggested that the infection of AdIκBα blocked NFκB activity in H460 cells and significantly inhibited cell proliferation by inducing apoptosis, which was confirmed by increased activity of caspase 3 in transfected cells. An in vivo study showed the tumor incidence to be significantly lower in mice implanted with H460 cells infected with AdIκBα than those with control virus (P = 0.012). For established H460 tumor, the intratumoral injection of AdIκBα also inhibited the tumor growth significantly. Immunohistochemical staining of treated tumor showed the suppressed VEGF expression. Conclusion. Overexpressed IκBα inhibited tumorigenesis significantly partly due to antiangiogenesis through the suppression of VEGF production. © 2005 The Japan Lung Cancer Society.