Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells
Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells
复制标题
木犀草素抑制前列腺癌细胞中的胰岛素样生长因子 1 受体信号传导
DOI：
10.1093/carcin/bgl189
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发表时间：
2007-03-01
期刊：
影响因子：
4.7
通讯作者：
Jiang, Bing-hua
中科院分区：
文献类型：
--
作者：
Fang, Jing;Zhou, Qiong;Jiang, Bing-hua
胰岛素样生长因子1受体（IGF-1 R）激活是前列腺细胞增殖所必需的。前列腺癌是西方国家最常见的恶性肿瘤之一。IGF-1 R在前列腺癌中的过表达与肿瘤生长相关。这些表明IGF-1 R抑制剂可能具有预防和/或治疗价值。随着黄酮类化合物的化学预防作用的证据越来越多，研究了一种生物活性黄酮类化合物木樨草素对前列腺癌细胞中IGF-1 R信号传导的影响。木犀草素抑制胰岛素样生长因子1（IGF-1）诱导的前列腺癌PC-3和DU 145细胞中IGF-1 R和AKT的激活。毛地黄黄酮对AKT的抑制导致其下游靶点磷酸化水平降低，包括p70 S6 K1、GSK-3 β和FKHR/FKHRL 1。木犀草素还抑制IGF-1诱导的EGFR和MAPK/ERK信号通路的激活。木犀草素抑制细胞周期蛋白D1的表达，增加p21的表达。结果，毛地黄黄酮抑制前列腺癌细胞增殖并诱导其凋亡。通过siRNA敲低IGF-1 R导致前列腺癌细胞增殖的抑制。体内肿瘤生长实验结果表明，木樨草素抑制PC-3肿瘤生长。肿瘤组织提取物的免疫印迹显示，木犀草素抑制IGF-1 R/AKT信号转导。我们的研究结果提供了一个新的洞察机制，木犀草素是对癌细胞。
Insulin-like growth factor 1 receptor (IGF-1R) activation is required for prostate cell proliferation. Prostate cancer is one of the most commonly diagnosed malignant tumors in Western countries. Overexpression of IGF-1R in prostate cancer is associated with tumor growth. These suggest that IGF-1R inhibitory agents may be of preventive and/or therapeutic value. With evidence accumulating for a chemopreventive role of flavonoids, the effects of luteolin, a bioactive flavonoid, on IGF-1R signaling in prostate cancer cells were examined. Luteolin inhibited insulin-like growth factor 1 (IGF-1) induced activation of IGF-1R and AKT in prostate cancer PC-3 and DU145 cells. Inhibition of AKT by luteolin resulted in decreased phosphorylation of its downstream targets, including p70S6K1, GSK-3 beta and FKHR/FKHRL1. Luteolin also inhibited the IGF-1-induced activation of EGFR and MAPK/ERK signaling. Luteolin inhibited expression of cyclin D1 and increased expression of p21. As a result, luteolin suppressed proliferation and induced apoptosis of prostate cancer cells. Knockdown of IGF-1R by siRNA led to inhibition of proliferation of prostate cancer cells. Results of in vivo tumor growth assay indicated that luteolin inhibited PC-3 tumor growth. Immunoblotting of the extracts of tumor tissues showed that luteolin inhibited IGF-1R/AKT signaling. Our results provide a new insight into the mechanisms that luteolin is against cancer cells.