Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 15, 2003; 9(5): 936-940
Published online May 15, 2003. doi: 10.3748/wjg.v9.i5.936
Synergistic effects of nimesulide and 5-fluorouracil on tumor growth and apoptosis in the implanted hepatoma in mice
Xiao-Hong Li, Xiao-Kun Li, Shao-Hui Cai, Fu-Xing Tang, Xue-Yun Zhong, Xian-Da Ren
Xiao-Hong Li, Shao-Hui Cai, Xian-Da Ren, Department of Pharmacokinetics, Pharmacy College, Jinan University, Guangzhou 510632, Guangdong Province, China
Xiao-Kun Li, Biopharmaceutical R&D Center of Jinan University, Guangzhou 510632, Guangdong Province, China
Fu-Xing Tang, Electron microscopy Center of Jinan University, Guangzhou 510632, Guangdong Province, China
Xue-Yun Zhong, Department of Pathology, Medical College, Jinan University, Guangzhou 510632, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No. 39770300, and the Overseas Chinese Affairs Office of the State Council Foundation, No. 98-33
Correspondence to: Professor Xian-Da Ren, Department of Pharmacokinetics, Pharmacy College, Jinan University, Guangzhou 510632, Guangdong, China. tsam@jnu.edu.cn
Telephone: +86-20-8522-0261
Received: November 26, 2002
Revised: December 9, 2002
Accepted: December 25, 2002
Published online: May 15, 2003
Abstract

AIM: 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. PGE2 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 PGE2 level was observed only for the treatment with nimesulide. No change was detected on c-fos expression.

CONCLUSION: 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.

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