Kaneuchi Masanori, Sasaki Masahiro, Tanaka Yuichiro, Sakuragi Noriaki, Fujimoto Seiichiro, Dahiya Rajvir
Department of Urology, University of California, and Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Int J Oncol. 2003 Jan;22(1):159-64.
Quercetin and other polyphenols have anti-carcinogenic and anti-tumorigenic activity in various organs, however, studies of this activity are lacking in endometrial cancer. We hypothesize that quercetin has anti-proliferative activity and the mechanisms of quercetin action may be through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with quercetin, and cell proliferation, expression of growth signal genes (EGF, VEGF, and TGF-alpha), cell cycle genes (p53, p21, p73, and cyclin D1), and apoptosis-related genes (bcl-2 and bax) were analyzed. Results of these experiments demonstrate that after a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1, whereas VEGF was up-regulated in Ishiwaka cell lines. Other genes such as TGF-alpha, p53, p21, p73, bcl-2 and bax were not significantly changed with quercetin treatment in Ishiwaka cell lines. The present study suggests that quercetin can suppress proliferation of Ishikawa cells through down-regulation of EGF and cyclin D1.
槲皮素和其他多酚类物质在多种器官中具有抗癌和抗肿瘤活性，然而，关于子宫内膜癌中这种活性的研究却很缺乏。我们推测槲皮素具有抗增殖活性，其作用机制可能是通过调节细胞周期和细胞生长调控基因。为了验证这一假设，我们用槲皮素处理子宫内膜癌细胞（石川细胞系），并分析了细胞增殖、生长信号基因（EGF、VEGF和TGF-α）、细胞周期基因（p53、p21、p73和细胞周期蛋白D1）以及凋亡相关基因（bcl-2和bax）的表达情况。这些实验结果表明，在分别用1、10和100微摩尔的槲皮素处理7天后，石川细胞的生长分别受到3%、51%和87%的抑制。基因和蛋白质表达数据表明，槲皮素处理（100微摩尔）显著降低了EGF和细胞周期蛋白D1的表达，而在石川细胞系中VEGF表达上调。其他基因，如TGF-α、p53、p21、p73、bcl-2和bax在石川细胞系中经槲皮素处理后没有显著变化。本研究表明，槲皮素可通过下调EGF和细胞周期蛋白D1来抑制石川细胞的增殖。
