Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.

Abstract

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.

• Authors: 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
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 12 Issue 42 Pg. 6766-70 (Nov 14 2006) ISSN: 1007-9327 [Print] United States
• PMID: 17106923 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• N3-o-toluyl-fluorouracil
• atofluding
• Fluorouracil

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Female
• Fluorouracil (analogs & derivatives, metabolism, pharmacology)
• Humans
• Liver (enzymology)
• Male
• Mice
• Mice, Nude
• Rats
• Rats, Sprague-Dawley
• Stomach Neoplasms (metabolism, pathology)
• Xenograft Model Antitumor Assays