title: Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Xu
authors.forename: Shu-Xiang
authors.initials: SX
authors.lastname: Cui
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Yuan
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Ruo-Han
authors.initials: RH
authors.lastname: Wang
authors.forename: Ruo-Yan
authors.initials: RY
authors.lastname: Gai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Qu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C517181:N3-o-toluyl-fluorouracil; C475762:atofluding; D005472:Fluorouracil