Peroxisome proliferator-activated receptors γ (
PPARγ) is a master regulator that controls
energy metabolism and
cell fate.
PPARγ2, a
PPARγ
isoform, is highly expressed in the normal
prostate but expressed at lower levels in
prostate cancer tissues. In the present study, PC3 and LNCaP
cells were used to examine the benefits of restoring
PPARγ2 activity.
PPARγ2 was overexpressed in PC3 and LNCaP
cells, and
cell proliferation and migration were detected.
Hematoxylin and
eosin (H&E)
staining was used to detect pathological changes. The
genes regulated by
PPARγ2 overexpression were detected by
microarray analysis. The restoration of
PPARγ2 in PC3 and LNCaP
cells inhibited
cell proliferation and migration. PC3-
PPARγ2
tissue recombinants showed
necrosis in cancerous regions and
leukocyte infiltration in the surrounding stroma by H&E
staining. We found higher mixed lineage
kinase domain-like (MLKL) and lower
microtubule-associated protein 1 light chain 3 (LC3) expression in
cancer tissues compared to controls by
immunohistochemistry (IHC)
staining.
Microarray analysis showed that
PPARγ2 gain of function in
PC3 cells resulted in the reprogramming of
lipid- and
energy metabolism-associated signaling pathways. These data indicate that
PPARγ2 exerts a crucial
tumor-suppressive effect by triggering
necrosis and an inflammatory reaction in
human prostate cancer.