Recently, the potential of PPAR-?? as a target for the prevention and treatment of cancer has been widely studied. However, the potential therapeutic role of PPAR-?? agonists has been questioned, based on contradictory results. Studies using animal models of colon cancer found that PPAR-?? agonists increased the development of colon tumors. This contradictory result was supplemented by a recent report using transgenic mice expressing a constitutive active form of PPAR-?? in mammary glands which showed that PPAR-?? signaling accelerated tumor development in mammary glands. The actual role of PPAR-?? in cancer has been complicated by recent findings that PPAR-?? agonists affect cancer cells independently of PPAR-??, and silencing of PPAR-?? and a PPAR-?? antagonist inhibit cancer cell growth. To date, the role of PPAR-?? in gastric carcinogenesis remains unclear.

A research article published in the World Journal of Gastroenterology addresses this question. A study from China found that PPAR-?? may be involved in gastric carcinogenesis, and that the PPAR-?? agonist 15d-PGJ2 may inhibit the growth of human gastric carcinoma MGC803 cell by inducing apoptosis and G1/G0 arrest, involving survivin, Skp2 and p27, but via a PPAR-??-independent pathway.

The study showed that the PPAR-?? agonist 15d-PGJ2 inhibited growth of cultured gastric cancer MGC803 cells, and demonstrated that the PPAR-?? antagonist GW9662 did not block this effect of 15d-PGJ2 and that 2.5 ??M GW9662 inhibited growth of MGC803 cells. Furthermore, PPAR-?? siRNA remarkably inhibited the growth of MGC803 cells.

These results indicated that 15d-PGJ2 inhibited growth of cultured gastric carcinoma MGC803 cells by a PPAR-??-independent pathway. These results also suggest that PPAR-?? agonists could be useful in the chemoprevention or chemotherapy of gastric malignancies.

Reference:
Ma XM, Yu H, Huai N. Peroxisome proliferator-activated receptor-g is essential in the pathogenesis of gastric carcinoma. World J Gastroenterol 2009; 15(31): 3874-3883 wjgnet/1007-9327/15/3874.asp