Inhibition of peroxisome proliferator-activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties.
Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARgamma is a nuclear receptor superfamily member that is expressed in many cancers. PPARgamma expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARgamma antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARgamma plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer.
Takahashi
Hirokazu
H
Gastroenterology Division, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
Fujita
Kouji
K
Fujisawa
Toshio
T
Yonemitsu
Kyoko
K
Tomimoto
Ayako
A
Ikeda
Ikuko
I
Yoneda
Masato
M
Masuda
Tomotaka
T
Schaefer
Katherine
K
Saubermann
Lawrence J
LJ
Shimamura
Takeshi
T
Saitoh
Satoru
S
Tachibana
Masashi
M
Wada
Koichiro
K
Nakagama
Hitoshi
H
Nakajima
Atsushi
A
D000199:Actins / Q000187:drug effects; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology
C457499:2-chloro-5-nitrobenzanilide; D000199:Actins; D000813:Anilides; D001549:Benzamides; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases