Increased expression of
vimentin in
carcinomas correlates with parameters of malignant potential such as
tumor grade and
tumor metastasis.
Peroxisome proliferator-activated receptor gamma (
PPARgamma) has been intensively evaluated as a potential target for the inhibition of cell growth and
metastasis in
cancer cells. In the present study, we examined whether
PPARgamma is a possible target molecule for the prevention of cell growth and invasion by treatment with agonists (
troglitazone,
rosiglitazone) and antagonists (
T0070907,
GW9662) in four different
hepatocellular carcinoma (HCC) cell lines. We also evaluated the effects of the
PPARgamma agonists and antagonists on
tumor cell migration and invasion. The expression level of
PPARgamma protein was higher in the sarcomatoid SH-J1 and poorly differentiated HLE cell lines than that in the well-differentiated HCC cell lines (HepG2 and Huh-7). Expression of
vimentin was high in the SH-J1 HCC cell line and minimally detected in the HLE cell line. Treatment with low doses of the
PPARgamma antagonists inhibited cell growth and colony formation of all four of the HCC cell lines.
Vimentin in the high-grade HCC cells was cleaved by the treatment with the
PPARgamma antagonists. Furthermore, treatment with the
PPARgamma antagonists also strongly inhibited migration and invasion of the SH-J1 and HLE cells. However, treatment with low doses of the agonists had no effect on
vimentin expression, migration, and invasion of the high-grade HCC cells but cell growth was inhibited by treatment with high concentrations of the agonists. Our results indicate that treatment with a
PPARgamma antagonist may prevent cell growth and invasion of high-grade HCC cells. Our findings also suggest that
PPARgamma antagonists inhibit cell growth and invasion through
vimentin disarrangement in high-grade HCC.