title: Chemopreventive effect of peroxisome proliferator-activated receptor gamma on gastric carcinogenesis in mice.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to be expressed in several cancers, and the treatment of these cancer cells with PPARgamma ligands often induces cell differentiation and apoptosis. Recently, the chemopreventive potential of PPARgamma ligands on colon carcinogenesis was reported, although the effect of PPARgamma on colon carcinogenesis and the mechanism of the effect remain controversial. In this study, we attempted to elucidate the role of PPARgamma in gastric carcinogenesis and explored the possible use of PPARgamma ligand as a chemopreventive agent for gastric cancer. N-methyl-N-nitrosourea (MNU, 240 ppm) was given in drinking water for 10 weeks to induce gastric cancer in PPARgamma wild-type (+/+) and heterozygous-deficient (+/-) mice, followed by treatment with PPARgamma ligand [troglitazone, 0.15% (w/w) in powder food] or the vehicle alone for 42 weeks. At the end of the experiment, PPARgamma (+/-) mice were more susceptible to MNU-induced gastric cancer than wild-type (+/+) mice (89.5%/55.5%), and troglitazone significantly reduced the incidence of gastric cancer in PPARgamma (+/+) mice (treatment 55.5%/vehicle 9%) but not in PPARgamma (+/-) mice. The present study showed that (a) PPARgamma suppresses gastric carcinogenesis, (b) the PPARgamma ligand troglitazone is a potential chemopreventive agent for gastric carcinogenesis, and (c) troglitazone's chemopreventive effect is dependent on PPARgamma.
authors.affiliation: Department of Gastrointestinal Surgery, Faculty of Medicine, University of Tokyo, Japan. jlu@east.ncc.go.jp
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imamura
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nomura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Mafune
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D002839:Chromans / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D008024:Ligands; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D002839:Chromans; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D008770:Methylnitrosourea; D000077288:Troglitazone