Synergistic effects of nimesulide and 5-fluorouracil on tumor growth and apoptosis in the implanted hepatoma in mice.
OBJECTIVE
To compare the effect of nimesulide or/and 5-fluorouracil (5-FU) on tumor growth inhibition and apoptosis in mice with the implanted hepatoma and to observe their possible interactions.


METHODS
The inhibitory effects on tumor growth was evaluated by inhibition rate. Apoptosis was assessed by the ultrastructural, flow cytometry features and the DNA ladder demonstrated by agarose gel electrophoresis. PGE(2) level was determined by radioimmunoassay. Expression levels of c-jun, c-fos and p53 were evaluated by western blotting.


RESULTS
Nimesulide or 5-FU alone inhibited the growth of hepatoma, while a synergistic effect was observed for a combined use of both. More pronounced morphologic changes for tumor cell apoptosis and the DNA ladder were found for the latter treatment. Expression levels of c-jun and p53 were found to be elevated for the tumors from mice treated with nimesulide and 5-FU comparing to those with either of them, but a reduced PGE(2) level was observed only for the treatment with nimesulide. No change was detected on c-fos expression.


CONCLUSIONS
Nimesulide and 5-FU appear to have synergistic effects for the growth inhibition and apoptosis induction. Both were found to be overexpressed in p53 and c-jun proteins, rather than that of c-fos, associations with the resulted apoptosis.
Li
Xiao-Hong
XH
Department of Pharmacokinetics, Pharmacy College, Jinan University, Guangzhou 510632, Guangdong Province, China.
Li
Xiao-Kun
XK
Cai
Shao-Hui
SH
Tang
Fu-Xing
FX
Zhong
Xue-Yun
XY
Ren
Xian-Da
XD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008854:Microscopy, Electron; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D016861:Cyclooxygenase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D015232:Dinoprostone; D005472:Fluorouracil; C012655:nimesulide