Do PPAR-g Agonists Have A Potential Therapeutic Role In Gastric Carcinoma?

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Colorectal Cancer;  Genetics;  Cancer / Oncology
Article Date: 27 Aug 2009 - 3:00 PDT

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Recently, the potential of PPAR-γ as a target for the prevention and treatment of cancer has been widely studied. However, the potential therapeutic role of PPAR-γ agonists has been questioned, based on contradictory results. Studies using animal models of colon cancer found that PPAR-γ 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-γ in mammary glands which showed that PPAR-γ signaling accelerated tumor development in mammary glands. The actual role of PPAR-γ in cancer has been complicated by recent findings that PPAR-γ agonists affect cancer cells independently of PPAR-γ, and silencing of PPAR-γ and a PPAR-γ antagonist inhibit cancer cell growth. To date, the role of PPAR-γ 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-γ may be involved in gastric carcinogenesis, and that the PPAR-γ 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-γ-independent pathway.

The study showed that the PPAR-γ agonist 15d-PGJ2 inhibited growth of cultured gastric cancer MGC803 cells, and demonstrated that the PPAR-γ antagonist GW9662 did not block this effect of 15d-PGJ2 and that 2.5 μM GW9662 inhibited growth of MGC803 cells. Furthermore, PPAR-γ 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-γ-independent pathway. These results also suggest that PPAR-γ 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 http://www.wjgnet.com/1007-9327/15/3874.asp

Source:
Lin Tian
World Journal of Gastroenterology