Knockdown of NF-κB p65 subunit expression suppresses growth of nude mouse lung tumor cell xenografts by activation of Bax apoptotic pathway

Nuclear factor-kappaB (NF-kappa B) is an important transcriptional factor and regulates a variety of pathophysiologic process involved in cell survival and death. The present study assesses the effects of NF-kappa B p65 subunit knockdown in suppression of nude mouse lung tumor cell xenografts and understands the underlying molecular events. A nude mouse Lewis lung carcinoma cell xenograft model was established and the mice were intraperitoneally injected with NF-kappa p65 siRNA and sacrificed after two weeks of tumor cell injection. Tumor xenografts were harvested for TUNEL, Western blot, and qRT-PCR analyses. Compared to the PBS-treated or the negative control (NC) siRNA-treated mice, tumor xenograft weight and volume was significantly decreased in the NF-kappa B p65 siRNA-treated mice. The TUNEL positive (apoptosis) cells in xenograft sections were 45 +/- 5 in PBS and 38 +/- 3 in NC siRNA, but increased to 271 +/- 11 in p65 siRNA-treated mice. Compared to the PBS or the NC mice, levels of Bax mRNA and protein in tumor xenografts were significantly upregulated in p65 siRNA-treated mice. Knockdown of NF-kappa 3 p65 subunit expression significantly inhibited the growth of nude mouse Lewis tumor cell xenografts by induction of tumor cell apoptosis and significantly up-regulation of pro-apoptotic protein Bax expression. Future study will confirm the current data and targeting NF-kappa B p65 subunit expression as a potential therapeutic strategy in treating human lung cancer.