Peritoneal metastasis inhibition by linoleic acid with activation of PPARgamma in human gastrointestinal cancer cells.
The effect on peritoneal metastasis of linoleic acid (LA) was examined using in vitro treatment of cancer cells and mouse peritoneal metastasis models. Firstly, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by LA in a dose-dependent manner with increment of apoptosis. LA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor gamma (PPARgamma) or 15-lipoxygenase-1, which converts LA to PPARgamma ligands. LA significantly inhibited invasion into type-IV collagen-coated membrane of MKN28 and Colo320 cells (p<0.05). BALB/c nu/nu mice inoculated with MKN28 and Colo320 cells into their peritoneal cavities were administrated with LA intraperitoneally (weekly, four times). The LA treatment significantly diminished the number of metastatic foci of both cells in the peritoneal cavity (p<0.05). Protein production in MKN28 and Colo320 cells treated with LA showed a decrease of epidermal growth factor receptor and an increase of Bax. These findings suggest that LA inhibits invasion and metastasis of human gastric and colon cancer cells by nondietary administration.
Sasaki
Takamitsu
T
Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
Fujii
Kiyomu
K
Yoshida
Kazuhiro
K
Shimura
Hideo
H
Sasahira
Tomonori
T
Ohmori
Hitoshi
H
Kuniyasu
Hiroki
H
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C494827:Bax protein, mouse; D016859:Lipoxygenase Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D047495:PPAR gamma; D051028:bcl-2-Associated X Protein; D019787:Linoleic Acid; D001093:Arachidonate 15-Lipoxygenase; D066246:ErbB Receptors