Aim: To examine the effect of a novel peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist TZD18 on cell proliferation and apoptosis in human glioblastoma T98G cells and its possible mechanism.
Methods: RT-PCR, MTT, TUNEL, Flow cytometry, and Western blot analysis were employed.
Results: TZD18 inhibited the growth of T98G cells in a concentration-dependent manner, which was associated with a G1 to S cell cycle arrest. Besides, significant apoptosis was induced after treatment with a non-toxic dose of TZD18. During the process, the expression of Bcl-2 protein was down-regulated, while that of Bax and p27kip proteins was up-regulated, and the activity of caspase-3 was elevated. However, this effect appeared to be PPARalpha and PPARgamma independent since their antagonists could not reverse this effect.
Conclusions: TZD18, a novel PPARalpha/gamma dual agonist, inhibited cell growth and induce apoptosis in human glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD18 in the treatment of glioblastoma.
Copyright 2004 Acta Pharmacologica Sinica