Nimesulide inhibits tumor growth in mice implanted hepatoma: overexpression of Bax over Bcl-2.

Abstract

AIM:

To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms.

METHODS:

Male mice received nimesulide 10 mg/kg, 20 mg/kg, and 40 mg/kg ig daily for 21 d. Electron microscopy (EM), flow cytometry (FCM), DNA ladder, radioimmunoassay (RIA), and Western blot analysis were employed to investigate effect of nimesulide on mice hepatoma and the related molecular mechanisms.

RESULTS:

Nimesulide inhibited the growth of hepatoma (from 14 % to 62 %) and elicited typical apoptotic morphologic changes. The DNA ladder of high dose nimesulide was more clearly observed and apoptotic rate was 51.3 %+/-1.5 %. Nimesulide also decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and Bcl-2 expression, while increased the level of Bax protein.

CONCLUSION:

Nimesulide suppresses tumor growth and induces apoptosis by inhibiting COX-2 and PGE2 expression, which may be related to overexpression of Bax over Bcl-2.

• Authors: Xiao-Hong Li, Jun-Jie Li, Hai-Wei Zhang, Peng Sun, Yan-Ling Zhang, Shao-Hui Cai, Xian-Da Ren
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 24 Issue 10 Pg. 1045-50 (Oct 2003) ISSN: 1671-4083 [Print] United States
• PMID: 14531950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bax protein, mouse
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Sulfonamides
• bcl-2-Associated X Protein
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone
• nimesulide

Topics

• Animals
• Apoptosis (drug effects)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (metabolism)
• Isoenzymes (metabolism)
• Liver Neoplasms, Experimental (metabolism, pathology)
• Male
• Mice
• Neoplasm Transplantation
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Random Allocation
• Sulfonamides (pharmacology)
• Tumor Cells, Cultured
• bcl-2-Associated X Protein