Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways.
Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways.
复制标题
DOI：
10.1371/journal.pone.0047516
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shi X
中科院分区：
文献类型：
--
作者：
Pratheeshkumar P;Budhraja A;Son YO;Wang X;Zhang Z;Ding S;Wang L;Hitron A;Lee JC;Xu M;Chen G;Luo J;Shi X
血管生成是癌症生长和转移的关键步骤，因为它使生长的肿瘤能够获得氧气和营养。使用天然产品预防癌症已成为癌症控制不可或缺的一部分。我们使用离体、体内和体外模型研究了槲皮素的抗血管生成活性。大鼠主动脉环实验表明，槲皮素在无毒浓度下可显著抑制微血管出芽，并对血管生成过程中的关键事件--内皮细胞的增殖、迁移、侵袭和管腔形成有显著抑制作用。最重要的是，槲皮素治疗抑制离体血管生成所揭示的鸡蛋绒毛尿囊膜测定（CAM）和基质胶塞测定。Western blot分析显示槲皮素抑制VEGF诱导的HUVECs中VEGF受体2及其下游蛋白激酶AKT、mTOR和核糖体蛋白S6激酶的磷酸化。槲皮素（20 mg/kg/d）显著降低前列腺异种移植瘤小鼠模型的实体瘤体积和重量，表明槲皮素通过靶向血管生成抑制肿瘤发生。槲皮素还可降低前列腺癌细胞的存活率，诱导细胞凋亡，其机制与下调AKT、mTOR和P70 S6 K的表达有关。槲皮素通过靶向VEGF-R2调控的AKT/mTOR/P70 S6 K信号通路抑制肿瘤生长和血管生成，有望成为肿瘤治疗的候选药物。
Angiogenesis is a crucial step in the growth and metastasis of cancers, since it enables the growing tumor to receive oxygen and nutrients. Cancer prevention using natural products has become an integral part of cancer control. We studied the antiangiogenic activity of quercetin using ex vivo, in vivo and in vitro models. Rat aortic ring assay showed that quercetin at non-toxic concentrations significantly inhibited microvessel sprouting and exhibited a significant inhibition in the proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Most importantly, quercetin treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Western blot analysis showed that quercetin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, mTOR, and ribosomal protein S6 kinase in HUVECs. Quercetin (20 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that quercetin inhibited tumorigenesis by targeting angiogenesis. Furthermore, quercetin reduced the cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, mTOR and P70S6K expressions. Collectively the findings in the present study suggest that quercetin inhibits tumor growth and angiogenesis by targeting VEGF-R2 regulated AKT/mTOR/P70S6K signaling pathway, and could be used as a potential drug candidate for cancer therapy.
登录
查看更多内容
影响因子：
11.2
作者：
Pang X;Yi Z;Zhang X;Sung B;Qu W;Lian X;Aggarwal BB;Liu M
通讯作者：
Liu M
DOI：
10.1615/jenvironpatholtoxicoloncol.v30.i1.40
发表时间：
2011-01-01
影响因子：
2.4
作者：
Pratheeshkumar, P.;Kuttan, Girija
通讯作者：
Kuttan, Girija
影响因子：
64.8
作者：
Risau, W
通讯作者：
Risau, W
内皮 p70 S6 激酶 1 调节肿瘤血管生成
影响因子：
11.2
作者：
Liu, Ling-Zhi;Zheng, Jenny Z.;Jiang, Bing-Hua
通讯作者：
Jiang, Bing-Hua
影响因子：
56.9
作者：
KECK, PJ;HAUSER, SD;CONNOLLY, DT
通讯作者：
CONNOLLY, DT