Inhibition of cell motility by troglitazone in human ovarian carcinoma cell line.
BACKGROUND
Troglitazone (TGZ) is a potential anticancer agent. Little is known about the effect of this agent on cancer cell migration.


METHODS
Human ovarian carcinoma cell line, ES-2 cells were treated with various concentrations of TGZ. Cell migration was evaluated by wound-healing and Boyden chamber transwell experiments. PPARgamma expression was blocked by PPARgamma small interfering RNA. The effects of TGZ on phosphorylation of FAK, PTEN, Akt were assessed by immunoblotting using phospho-specific antibodies. The cellular distribution of paxillin, vinculin, stress fiber and PTEN was assessed by immunocytochemistry.


RESULTS
TGZ dose- and time-dependently impaired cell migration through a PPARgamma independent manner. TGZ treatment impaired cell spreading, stress fiber formation, tyrosine phosphorylation of focal adhesion kinase (FAK), and focal adhesion assembly in cells grown on fibronectin substratum. TGZ also dose- and time-dependently suppressed FAK autophosphorylation and phosphorylation of the C-terminal of PTEN (a phosphatase). At concentration higher than 10 muM, TGZ caused accumulation of PTEN in plasma membrane, a sign of PTEN activation.


CONCLUSIONS
These results indicate that TGZ can suppress cultured ES-2 cells migration. Our data suggest that the anti-migration potential of TGZ involves in regulations of FAK and PTEN activity.
Yang
Yuh-Cheng
YC
Mackay Medicine, Nursing and Management College, Taipei, Taiwan. eugene@ms2.mmh.org.tw
Ho
Tsung-Chuan
TC
Chen
Show-Li
SL
Lai
Huei-Yi
HY
Wu
Ju-Yun
JY
Tsao
Yeou-Ping
YP
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D000077288:Troglitazone
D002839:Chromans; D045162:Thiazolidinediones; D000077288:Troglitazone