Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells.
The effect of conjugated linoleic acid (CLA) on peritoneal metastasis was examined by in vitro treatment of cancer cells and mouse peritoneal metastasis models. First, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by CLA in a dose-dependent manner with an increment in apoptosis. CLA significantly inhibited invasion into type IV collagen-coated membrane of MKN28 and Colo320 cells (p < 0.05). CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma in both cell lines. BALB/c nu-nu mice were inoculated with MKN28 and Colo320 cells into their peritoneal cavity, and administrated with CLA intraperitoneally (weekly, 4 times). CLA treatment did not affect food intake or weight gain of mice. CLA treatment significantly decreased metastatic foci of both cells in the peritoneal cavity (p < 0.005). Survival rate in mice inoculated with MKN28 or Colo320 cells was significantly recovered by CLA treatment (p = 0.0025 and 0.0052, respectively). Protein production in MKN28 and Colo320 cells treated with CLA showed a decrease in epidermal growth factor receptor and transforming growth factor-alpha and an increase in Bax. These findings suggest that CLA inhibits metastasis of human gastric and colon cancer cells.
Kuniyasu
Hiroki
H
Department of Molecular Pathology, Nara Medical University, Kashihara, Japan. cooninh@zb4.so-net.ne.jp
Yoshida
Kazuhiro
K
Sasaki
Takamitsu
T
Sasahira
Tomonori
T
Fujii
Kiyomu
K
Ohmori
Hitoshi
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors; D006801:Humans; D007274:Injections, Intraperitoneal; D044243:Linoleic Acids, Conjugated / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D016211:Transforming Growth Factor alpha; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D044243:Linoleic Acids, Conjugated; D020319:Oligodeoxyribonucleotides, Antisense; D047495:PPAR gamma; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D051028:bcl-2-Associated X Protein; D066246:ErbB Receptors