Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines
Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines
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DOI：
10.1016/j.tox.2007.10.023
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发表时间：
2008-01-14
期刊：
影响因子：
4.5
通讯作者：
Peters, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Girroir, Elizabeth E.;Hollingshead, Holly E.;Peters, Jeffrey M.
用于治疗包括代谢综合征、糖尿病和肥胖症在内的疾病的过氧化物酶体增殖物激活受体-β/δ（PPARbeta/delta）配体的开发由于其潜在安全性的矛盾发现而受到阻碍。例如，虽然一些报告显示，PPAR β/δ的配体活化促进终末分化的诱导和细胞生长的抑制，但其他报告表明，PPAR β/δ配体通过增加细胞增殖而增强肿瘤发生。一些相互矛盾的结果可能部分是由于检查的配体的差异、细胞培养物中是否存在血清、细胞系的差异或用于定量细胞生长的方法的差异。由于这些原因，本研究使用两种高度特异性的PPARbeta/delta配体GW 0742或GW 501516，在存在或不存在血清的情况下，检查了PPARbeta/delta的配体活化对两种人癌细胞系MCF 7（乳腺癌）和UACC 903（黑色素瘤）的细胞生长的影响。在存在GW 0742或GW 501516的情况下培养细胞引起已知的PPAR β/δ靶基因血管生成素样蛋白4（ANGPTL 4）的上调。在存在GW 0742或GW 501516的情况下培养的两种细胞系中均观察到细胞生长的抑制，并且血清的存在或不存在对这种抑制几乎没有影响。本研究的结果表明，PPAR β/δ的配体活化抑制MCF 7和UACC 903细胞系的生长，并提供了进一步的证据，证明PPAR β/δ配体在人类癌细胞系中不具有促有丝分裂作用。出版社：Elsevier爱尔兰Ltd.
The development of peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPAR beta/delta promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPAR beta/delta ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPAR beta/delta on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPAR beta/delta ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPAR beta/delta target gene angiopoiefin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPAR beta/delta inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPAR beta/delta ligands are not mitogenic in human cancer cell lines. Published by Elsevier Ireland Ltd.