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


CONCLUSIONS
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.
Li
Xiao-Hong
XH
Department of Pharmacokinetics, Pharmacy College, Ji-nan University, Guangzhou 510632, China. Tsam@jnu.edu.cn
Li
Jun-Jie
JJ
Zhang
Hai-Wei
HW
Sun
Peng
P
Zhang
Yan-Ling
YL
Cai
Shao-Hui
SH
Ren
Xian-Da
XD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011897:Random Allocation; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C012655:nimesulide