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©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil
Jian Liu, Wen-Fang Xu, Shu-Xiang Cui, Yong Zhou, Yun-Xia Yuan, Ming-Hui Chen, Ruo-Han Wang, Ruo-Yan Gai, Masatoshi Makuuchi, Wei Tang, Xian-Jun Qu
Jian Liu, Wen-Fang Xu, Yun-Xia Yuan, Ming-Hui Chen, Wei Tang, Xian-Jun Qu, Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, China
Jian Liu, Department of Pharmacy, Second Affiliated Hospital, Shandong Traditional Chinese Medical University, Jinan 250001, Shandong Province, China
Shu-Xiang Cui, Ruo-Han Wang, Department of Pharmacology, The Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062, Shandong Province, China
Yong Zhou, Center for Drug Evaluation and Certification of Shandong, Jinan 250014, Shandong Province, China
Ruo-Yan Gai, Masatoshi Makuuchi, Wei Tang, Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No.30472038; Department of Science and Technology of Shandong Province, China and Japan-China Medical Association
Correspondence to: Dr. Xian-Jun Qu, Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China. qxj@sdu.edu.cn
Telephone: +86-531-88382542 Fax: +86-531-88382542
Received: March 20, 2006
Revised: August 5, 2006
Accepted: August 13, 2006
Published online: November 14, 2006
AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45.
METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo.
RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight.
CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.
