Inhibition of cell invasion and morphological change by troglitazone in human pancreatic cancer cells.
BACKGROUND
We have recently demonstrated that peroxisome proliferator activated receptor (PPAR) gamma activation by its selective ligand, troglitazone, potently inhibited cell proliferation in human pancreatic cancer cells. The present study was performed to clarify the role of PPARgamma in cell invasion/motility in human pancreatic cancer cells.


METHODS
Cell invasive activity was assessed by an in vitro invasion assay, using a Transwell chamber, and by a wound-healing assay, in the human pancreatic cancer cell lines, PK-1 and PK-9. Cell morphology and actin structure were evaluated by phase-contrast and fluorescence microscopy.


RESULTS
PPARgamma activation by troglitazone inhibited cell invasion and cell migration in PK-1 and PK-9 cells. We also examined the effect of troglitazone on cell morphology and actin structure because of its effect on cell motility. The size of PK-1 and PK-9 cells that had been incubated with troglitazone became smaller, and the in shape changed from flat to spindle, followed by round. The troglitazone-induced cell rounding was reversible by replacement with troglitazone-free medium. Rhodamine-phalloidin staining revealed a decreased number of actin filaments in PK-1 cells treated with troglitazone. In cells treated with mycalolide B, an actin depolymerizing agent, troglitazone failed to induce cell rounding.


CONCLUSIONS
These results suggest that PPARgamma activation by troglitazone inhibited cell motility and changed cell morphology through modulating actin organization.
Motomura
Wataru
W
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Nagamine
Miho
M
Tanno
Satoshi
S
Sawamukai
Mitsuko
M
Takahashi
Nobuhiko
N
Kohgo
Yutaka
Y
Okumura
Toshikatsu
T
D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D003599:Cytoskeleton / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000502:physiology*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
D000199:Actins; D000970:Antineoplastic Agents; D002839:Chromans; D017077:Culture Media, Conditioned; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone