Peroxisome proliferator-activated receptor-gamma is essential in the pathogenesis of gastric carcinoma.
OBJECTIVE
To investigate whether peroxisome proliferator-activated receptor gamma (PPAR-gamma) is expressed in human gastric carcinoma and whether PPAR-gamma is a potential target for gastric carcinoma therapy.


METHODS
PPAR-gamma protein in gastric carcinoma was examined by immunohistochemistry. In the gastric carcinoma cell line MGC803, PPAR-gamma, survivin, Skp2 and p27 protein and mRNA were examined by Western blotting and real-time reverse transcription-polymerase chain reaction, respectively; proliferation was examined by MTT; apoptosis was examined by chromatin staining with Hoechst 33342 and fluorescence activated cell sorting (FACS). and cell cycle was examined by FACS; the knockdown of PPAR-gamma was done by RNA interference.


RESULTS
A high level of expression of PPAR-gamma was observed in human gastric carcinoma and in a human gastric carcinoma cell line MGC803. The PPAR-gamma agonist 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) inhibited growth, and induced apoptosis and G(1)/G(0) cell cycle arrest in MGC803 cells in a concentration-dependent and time-dependent manner. The effect of 15d-PGJ(2) on MGC803 cells was not reversed by the selective and irreversible antagonist GW9662 for PPAR-gamma. Furthermore, survivin and Skp2 expression were decreased, whereas p27 expression was enhanced following 15d-PGJ(2) treatment in a dose-dependent manner in MGC803 cells. Interestingly, we also found that small interfering RNA for PPAR-gamma inhibited growth and induced apoptosis in MGC803 cells. The inhibition of PPAR-gamma function may be a potentially important and novel modality for treatment and prevention of gastric carcinoma.


CONCLUSIONS
A PPAR-gamma agonist inhibited growth of human gastric carcinoma MGC803 cells by inducing apoptosis and G(1)/G(0) cell cycle arrest with the involvement of survivin, Skp2 and p27 and not via PPAR-gamma.
Ma
Xiu-Mei
XM
Department of Pathology, The First Affiliated Hospital of Inner Mongolia Medical College, Huhhot 010059, Inner Mongolia Autonomous Region, China. maxiumei0471@yahoo.com.cn
Yu
Hong
H
Huai
Na
N
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077022:Survivin
C097240:15-deoxy-delta(12,14)-prostaglandin J2; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins; D000077022:Survivin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015230:Prostaglandin D2
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