Li Y-S, Wu L-P, Li K-H, Liu Y-P, Xiang R, Zhang S-B, Zhu L-Y, Zhang L-Y
Department of Orthopaedics, Xiangya Hospital, Shenzhen, China.
J Int Med Res. 2011;39(6):2141-50. doi: 10.1177/147323001103900610.
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.
染料木黄酮可抑制多种人类癌细胞系的生长，但其作用机制尚不清楚。本研究确定染料木黄酮的作用是否通过抑制环氧化酶（COX）-2蛋白介导，并阐明其在人胃癌细胞系BGC-823中的作用机制。染料木黄酮处理以剂量和时间依赖性方式抑制细胞增殖并诱导凋亡；蛋白质印迹分析表明COX-2蛋白水平呈显著的剂量依赖性降低。染料木黄酮处理对转录因子核因子κB（NF-κB）的激活具有显著抑制作用。此外，NF-κB抑制剂吡咯烷二硫代氨基甲酸盐可导致COX-2蛋白水平降低和NF-κB激活受抑制，类似于染料木黄酮的作用。COX-2蛋白的抑制可能对染料木黄酮在BGC-823细胞中的抗增殖和促凋亡作用很重要，且这些作用可能部分通过NF-κB途径介导。
