BAY 11-7082, a nuclear factor-κB inhibitor, induces apoptosis and S phase arrest in gastric cancer cells

Background: Inhibitors of nuclear factor (NF)-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in gastric Cancer.

Methods: Firstly, we screened the inhibitory effect of pharmacologic NF-κB inhibitors on cell viability of human gastric Cancer cells via CCK-8 assay. Next, cell Apoptosis, cell cycle distribution, and mitochondrial membrane potential after BAY 11-7082 treatment were detected by annexin V staining, propidium iodide staining, TUNEL, and JC-1 assays in human gastric Cancer HGC-27 cells. Expression of regulatory factors for Apoptosis and cell cycle were measured by western blot. Finally, human gastric Cancer xenograft model was established to verify the anti-tumor effects of BAY 11-7082 in vivo. Cellular Apoptosis and growth inhibition in subcutaneous tumor section were detected by TUNEL and immunohistochemistry assays.

Results: BAY 11-7082 exhibited rapid and potent anti-tumor effects on gastric Cancer cells in vitro within a panel of NF-κB inhibitors. BAY 11-7082 induced rapid Apoptosis in HGC-27 cells through activating the mitochondrial pathway, as well as down-regulation of Bcl-2 and up-regulation of Bax. BAY 11-7082 also induced S phase arrest through suppressing Cyclin A and CDK-2 expression. Xenograft model confirmed the anti-tumor effects of BAY 11-7082 on Apoptosis induction and growth inhibition in vivo.

Conclusions: Our results demonstrated that BAY 11-7082 presented the most rapid and potent anti-tumor effects within a panel of NF-κB inhibitors, and could induce cellular Apoptosis and block cell cycle progression both in vitro and in vivo, thus providing basis for clinical application of BAY 11-7082 in gastric Cancer cases.