Peroxisome proliferator-activated receptor-γ and growth inhibition by its ligands in prostate cancer

过氧化物酶体增殖物激活受体-γ (PPAR-γ)在某些人类癌症中表达。配体诱导的PPAR-γ激活可导致这些癌细胞的生长抑制和分化；然而，PPAR-γ配体抗增殖作用的确切机制尚不清楚。本研究旨在探讨PPAR-γ在人前列腺癌中的表达及PPAR-y配体对前列腺癌细胞生长的影响。PPAR-γ在雄激素不依赖型前列腺癌细胞系和人前列腺癌组织中经常过表达（22 / 47;47%）。研究了PPAR-γ配体15 - deoxy-deltal2、14 -前列腺素J2 （15d-PGJ2）和曲格列酮对前列腺癌细胞生长的影响。15d-PGJ2和曲格列酮均能抑制前列腺癌细胞的增殖和DNA合成，且呈剂量依赖性，并能略微增加S期DNA含量的细胞比例。PSA启动子报告基因实验显示，曲格列酮和15d-PGJ2下调LNCaP中雄激素刺激的报告基因活性。PSA启动子包含8个雄激素受体反应元件。有趣的是，LNCaP联合曲格列酮显著抑制PSA蛋白表达，但不抑制AR表达。综上所述，这些结果表明PPAR-γ配体可能是治疗前列腺癌的有效药物。

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is expressed in certain human cancers. Ligand-induced PPAR-γ activation can result in growth inhibition and differentiation in these cancer cells ; however, the precise mechanism for the anti-proliferative effect of PPAR-γ ligands is not clear. This study aimed to examine the expression of PPAR-γ in human prostate cancer and the effect of PPAR-y ligands on prostate cancer cell growth. PPAR-γ is frequently overexpressed in androgen independent prostate cancer cell lines and human prostate cancer tissues (22 of 47 ; 47%). The effect of two PPAR-γ ligands, 15 deoxy-deltal2, 14 prostaglandin J2 (15d-PGJ2) and troglitazone, on the growth of a prostate cancer cell line was assessed. Both 15d-PGJ2 and troglitazone inhibited proliferation and DNA synthesis of prostate cancer cell lines in a dose-dependent manner, and slightly increased the proportion of cells with S phase DNA content. PSA promoter reporter assays showed that troglitazone and 15d-PGJ2 down-regulated androgen stimulated reporter gene activity in LNCaP. The PSA promoter contains eight androgen receptor response elements. Interestingly, LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression. Taken together, these results suggest that PPAR-γ ligands may be a useful therapeutic agent for the treatment of prostate cancer.