Journal of International Medical Research, 2011, 39(6):2141-50.

Involvement of Nuclear Factor κB (NF-κB) in the Downregulation of Cyclooxygenase-2 (COX-2) by Genistein in Gastric Cancer Cells

Li Y S, Wu L P, Li K H, et al

Department of Orthopaedics, Xiangya Hospital, Shenzhen, China; et al

Genistein induces growth inhibition in various human cancer cell lines but its mechanism of action remains unknown. This study determined whether the effect of genistein is mediated via suppression of cyclo-oxygenase (COX)-2 protein, and elucidated the mechanism of action of this effect in the human gastric cancer cell line BGC-823. Genistein treatment inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner; Western blotting analysis indicated a significant dose-dependent decrease in COX-2 protein levels. Genistein treatment exerted a significant inhibitory effect on activation of the transcription factor nuclear factor κB (NF-κB). Additionally, the NF-κB inhibitor pyrrolidine dithiocarbamate caused a reduction in COX-2 protein levels and NF-κB activation, similar to the effect of genistein. Suppression of COX-2 protein may be important for the antiproliferative and proapoptotic effects of genistein in BGC-823 cells, and these effects may be partly mediated through the NF-κB pathway.

英国《国际医学研究杂志》，2011年

在胃癌细胞中细胞核因子 κB (NF-κB) 参与染料木黄酮对环氧合酶-2 (COX-2) 的下调

李YS，吴LP，李KH等

中国深圳湘雅医院骨科等

染料木黄酮诱导多种人体肿瘤细胞的生长抑制，但其作用机理仍然未知。本研究确定了染料木黄酮的作用是否通过抑制环氧化酶 (COX)-2 介导蛋白调节，并阐明了这种效应在人体胃癌细胞 BGC- 823 中的作用机制。金雀异黄素治疗以依赖剂量和时间的方式抑制细胞增殖并诱导凋亡；免疫印迹分析表明环氧合酶-2 蛋白质的水平明显剂量依赖性的降低。金雀异黄素治疗对转录因子核因子 κB (NF-κB)的活化产生明显的抑制作用。此外，NF-κ B 抑制剂吡咯烷硫代氨基甲酸导致环氧合酶-2 的蛋白水平降低， NF-κ B 的激活，与染料木黄酮的作用类似。环氧合酶-2 蛋白的抑制对于染料木黄酮影响人体胃癌BGC-823 细胞的抗增殖和凋亡可能比较重要，并且这些影响可能部分通过NF-κ B 途径介导。