Brockman J A, Gupta R A, Dubois R N
Gastroenterology Division, Departments of Medicine and Cell Biology, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee, USA.
Gastroenterology. 1998 Nov;115(5):1049-55. doi: 10.1016/s0016-5085(98)70072-1.
BACKGROUND & AIMS: Peroxisomal proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that provides a direct link between fatty acid metabolism and control of gene transcription. The objective of this study was to determine the biological effect(s) of PPARgamma activation in colorectal carcinoma cells.
PPARgamma expression and activity were measured in 4 human colon cancer cell lines using reverse-transcription polymerase chain reaction, immunoprecipitation and immunoblotting, and transient reporter gene assays. The effects of activated PPARgamma in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPARgamma activation on progression through the cell cycle.
PPARgamma was expressed in all 4 colon cancer cell lines examined and was transcriptionally functional in 3 of the 4. Treatment of these cells with a selective PPARgamma activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPARgamma present. Finally, activation of PPARgamma resulted in G1 cell cycle arrest.
Activation of the PPARgamma pathway in colon cancer cells has potent antiproliferative effects, suggesting that this nuclear hormone receptor may provide a novel target for prevention and treatment of colorectal cancer in humans.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种核激素受体，它在脂肪酸代谢与基因转录调控之间建立了直接联系。本研究的目的是确定PPARγ激活在结肠癌细胞中的生物学效应。
使用逆转录聚合酶链反应、免疫沉淀和免疫印迹以及瞬时报告基因分析，在4种人结肠癌细胞系中检测PPARγ的表达和活性。通过细胞增殖和非锚定依赖性生长分析评估激活的PPARγ在这些细胞系中的作用。采用流式细胞术确定PPARγ激活对细胞周期进程的影响。
在所检测的所有4种结肠癌细胞系中均表达PPARγ，并且在其中3种细胞系中具有转录功能。用选择性PPARγ激活剂（BRL 49653）处理这些细胞导致非锚定依赖性生长受到抑制。生长抑制程度与存在的功能性PPARγ水平相关。最后，PPARγ激活导致G1期细胞周期停滞。
结肠癌细胞中PPARγ途径的激活具有强大的抗增殖作用，表明这种核激素受体可能为人类结直肠癌的预防和治疗提供一个新靶点。
