Gastric Cancer
Copyright ©The Author(s) 2002. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2002; 8(3): 431-435
Published online Jun 15, 2002. doi: 10.3748/wjg.v8.i3.431
Changes of NF-κB, p53, Bcl-2 and caspase in apoptosis induced by JTE-522 in human gastric adenocarcinoma cell line AGS cells: role of reactive oxygen species
Hong-Liang Li, Dan-Dan Chen, Xiao-Hong Li, Hai-Wei Zhang, Yan-Qing Lü, Chun-Ling Ye, Xian-Da Ren
Hong-Liang Li, Xiao-Hong Li, Yan-Qing Lü, Chun-Ling Ye, Xian-Da Ren, Department of Pharmacology, Jinan University Pharmacy College, Guangzhou 510632, Guangdong, China
Dan-Dan Chen, Department of Cardiology, First Affiliated Hospital, Zhongshan University, Guangzhou 510089, Guangdong, China
Hai-Wei Zhang, Department of Pathology, Jinan University Medical College, Guangzhou 510632, Guangdong, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No. 39770300, 30070873, and the Overseas Chinese Affairs Office of the State Council Foundation, No. 98-33
Correspondence to: Prof. Xian-Da Ren, Department of Pharmacology, Jinan University Pharmacy College, Guangzhou 510632, Guangdong, China.
Telephone: +86-20-85220261
Received: January 28, 2002
Revised: February 14, 2002
Accepted: March 5, 2002
Published online: June 15, 2002

AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-κB, p53, bcl-2 and caspase in the apoptosis process.

METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms.

RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-κB activity was almost completely inhibited by preventing the degradation of IkBα. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner.

CONCLUSION: These findings suggest that reactive oxygen species, NF-κB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.

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