Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
Oncol Rep. 2011 Aug;26(2):447-53. doi: 10.3892/or.2011.1321. Epub 2011 May 26.
In the present study, we investigated the effects of fenofibrate on the invasive potential of DU-145 human prostate cancer cells in the context of gap junctional intercellular coupling and the formation of reactive oxygen species. Time-lapse analyses of cell motility, accompanied by tests of cell viability, membrane microviscosity, reactive oxygen species accumulation and the function of gap junctional protein connexin 43 were performed in monolayer cultures of DU-145 cells following fenofibrate administration. Fenofibrate inhibited the motility of DU-145 cells and attenuated gap junctional intercellular coupling in a manner independent of its effects on cell viability, PPARα activation and cell membrane micro-viscosity. Instead, N-acetyl-L-cysteine, a scavenger of reactive oxygen species, restored cell motility and gap junctional coupling in fenofibrate-treated DU-145 cell populations. These data indicate that two parameters crucial for cancer cell metastatic potential, i.e. cell motility and gap junctional coupling, are inhibited by fenofibrate. Thus, fenofibrate affects prostate cancer cell invasion via an orchestrated action on versatile cancer cell properties determining this process. A novel mechanism of anti-invasive activity of fenofibrate, which depends on its interference with cell motility and the function of gap junctions regulated by reactive oxygen species, is suggested.
在本研究中，我们研究了非诺贝特在缝隙连接细胞间偶联和活性氧形成的背景下对 DU-145 人前列腺癌细胞侵袭潜力的影响。在单层 DU-145 细胞培养中，通过细胞迁移的时差分析，伴随着细胞活力、膜微粘度、活性氧积累和缝隙连接蛋白连接蛋白 43 功能的测试，进行了非诺贝特给药后的研究。非诺贝特抑制 DU-145 细胞的迁移，并以不依赖于其对细胞活力、PPARα 激活和细胞膜微粘度的影响的方式减弱缝隙连接细胞间偶联。相反，活性氧清除剂 N-乙酰-L-半胱氨酸恢复了非诺贝特处理的 DU-145 细胞群体中的细胞迁移和缝隙连接偶联。这些数据表明，两种对癌细胞转移潜力至关重要的参数，即细胞迁移和缝隙连接偶联，被非诺贝特抑制。因此，非诺贝特通过对决定这一过程的多种癌细胞特性的协调作用影响前列腺癌细胞的侵袭。提出了非诺贝特抗侵袭活性的新机制，该机制依赖于其对细胞迁移和活性氧调节的缝隙连接功能的干扰。
