Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.
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.
Liu
Jian
J
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China.
Xu
Wen-Fang
WF
Cui
Shu-Xiang
SX
Zhou
Yong
Y
Yuan
Yun-Xia
YX
Chen
Ming-Hui
MH
Wang
Ruo-Han
RH
Gai
Ruo-Yan
RY
Makuuchi
Masatoshi
M
Tang
Wei
W
Qu
Xian-Jun
XJ
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
D000970:Antineoplastic Agents; C517181:N3-o-toluyl-fluorouracil; C475762:atofluding; D005472:Fluorouracil