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

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.

• Authors: Ling Chen, Yuanyuan Ruan, Xuefei Wang, Lingqiang Min, Zhenbin Shen, Yihong Sun, Xinyu Qin
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 49 Issue 5 Pg. 864-74 (May 2014) ISSN: 1435-5922 [Electronic] Japan
• PMID: 23846545 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• Antineoplastic Agents
• NF-kappa B
• Nitriles
• Sulfones

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• In Situ Nick-End Labeling
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• NF-kappa B (antagonists & inhibitors)
• Nitriles (pharmacology)
• S Phase Cell Cycle Checkpoints (drug effects)
• Stomach Neoplasms (drug therapy, pathology)
• Sulfones (pharmacology)
• Up-Regulation (drug effects)
• Xenograft Model Antitumor Assays