Inhibition of human gastric carcinoma cell growth by atofluding derivative N_3-o-toluyl-fluorouracil  

作　　者：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 

机构地区：[1]Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, China [2]Department of Pharmacy, Second Affiliated Hospital, Shandong Traditional Chinese Medical University, Jinan 250001, Shandong Province, China [3]Department of Pharmacology, The Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062, Shandong Province, China [4]Center for Drug Evvaluation and Certification of Shandong, Jinan 250014, Shandong Province, China [5]Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 113-8655, Tokyo, Japan

出　　处：《World Journal of Gastroenterology》2006年第42期6766-6770,共5页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China, No.30472038; Department of Science and Technology of Shandong Province, China and Japan-China Medical Association

摘　　要：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 v/vo, 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.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 welltolerated 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.

关 键 词：N3-o-toluyl-fluorouracil Gastric carcinoma cells PRO-DRUG Growth inhibition 

分 类 号：R735.2[医药卫生—肿瘤]