A novel PPAR alpha/gamma dual agonist inhibits cell growth and induces apoptosis in human glioblasto

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:coni
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AIM: To examine the effect of a novel peroxisome proliferator-activated receptor (PPAR) α/γ 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 Gl 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 PPARa and PPARy independent since their antagonists could not reverse this effect. CONCLUSIONS: TZD18, a novel PPARα/γ dual agonist, inhibited cell growth and induce apoptosis in human glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD18 in the treatment 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 the 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 was reported to PPARa and PPARy independent from their antagonists could not reverse this effect. CONCLUSIONS: TZD18, a novel PPARα / γ dual agonist, inhibited cell growth and induce apoptosis in human glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD 18 in the treatment
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