Implication of peroxisome proliferator-activated receptor gamma and proinflammatory cytokines in gastric carcinogenesis: link to Helicobacter pylori-infection.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor involved in various processes including the inflammation and carcinogenesis. The aim of the present study was 1) to examine the mRNA and protein expression of PPARgamma in gastric cancer (GC); 2) to evaluate the effect of PPARgamma ligand (ciglitazone) on the proliferation and apoptosis of GC cell line; and 3) to assess the levels of gastric tissue proinflammatory cytokines, IL-1beta and IL-8, and plasma gastrin in GC patients before and after Helicobacter pylori (H. pylori) eradication. The trial material included 30 H. pylori-negative controls and 30 sex- and age-matched GC patients without or with H. pylori before and after its eradication. Expression of tissue PPARgamma, tissue levels of IL-1beta and IL-8, and plasma concentration of gastrin were significantly higher in H. pylori-positive GC compared to controls, but H. pylori eradication significantly reduced these parameters. Kato III cells incubated with alive H. pylori upregulated PPARgamma expression and ciglitazone inhibited cell proliferation and induced apoptosis. PPARgamma, proinflammatory cytokines and plasma gastrin appear to be implicated in H. pylori-related gastric carcinogenesis and PPARgamma agonists may have potential in cancer therapy.
Konturek
Peter C
PC
Department of Medicine I, University Erlangen-Nuernberg, Ulmenweg 18, 91054 Erlangen, Germany. Peter.Konturek@med1.imed.uni-erlangen.de
Kania
Joanna
J
Kukharsky
Vitaly
V
Raithel
Martin
M
Ocker
Mathias
M
Rembiasz
Kazimierz
K
Hahn
Eckhart G
EG
Konturek
Stanislaw J
SJ
D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D045162:Thiazolidinediones / Q000494:pharmacology
D016207:Cytokines; D047495:PPAR gamma; D045162:Thiazolidinediones; C039671:ciglitazone