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BAY 11-7082, a Nuclear factor-κB Inhibitor, Induces Apoptosis and S Phase Arrest in Gastric Cancer Cells

BAY 11-7082, a Nuclear factor-κB Inhibitor, Induces Apoptosis and S Phase Arrest in Gastric Cancer Cells

Ling Chen, Yuanyuan Ruan, Xuefei Wang, Lingqiang Min, Zhenbin Shen, Yihong Sun, Xinyu Qin

J Gastroenterol. 2014 May;49(5):864-74.

PMID: 23846545

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP19542677	Bay 11-7082		19542-67-7	Price

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