Knockdown of NF-κB p65 subunit expression suppresses growth of nude mouse lung tumor cell xenografts by activation of Bax apoptotic pathway
Abstract:
Nuclear factor-kappaB (NF-κB) 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-κB 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-κB 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-κB 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-κB 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-κB p65 subunit expression as a potential therapeutic strategy in treating human lung cancer.