Glaucarubinone inhibits colorectal cancer growth by suppression of hypoxia-inducible factor 1α and β-catenin via a p-21 activated kinase 1-dependent pathway.
Glaucarubinone inhibits colorectal cancer growth by suppression of hypoxia-inducible factor 1α and β-catenin via a p-21 activated kinase 1-dependent pathway.
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素carubinone通过P-21激活的激酶1依赖性途径抑制缺氧诱导因子1α和β-catenin抑制结直肠癌的生长。
DOI：
10.1016/j.bbamcr.2014.10.013
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
He H
中科院分区：
文献类型：
--
作者：
Huynh N;Beutler JA;Shulkes A;Baldwin GS;He H
p-21 激活激酶 1 (PAK1) 通过刺激 Wnt/β-连环蛋白、ERK 和 AKT 通路来促进结直肠癌 (CRC) 进展。 PAK1 还通过上调缺氧诱导因子 1α (HIF-1α)（癌症存活的关键因素）来促进 CRC 存活。 Glaucarubinone 是一种苦木素天然产物，通过下调 PAK1 抑制胰腺癌生长。本研究的目的是探讨青光红酮对结直肠癌生长和转移的影响及其机制。在体外通过[3H]-胸苷掺入测量细胞增殖，在体内通过肿瘤异种移植物的体积测量细胞增殖。通过细胞提取物的蛋白质印迹测量蛋白质浓度。我们在此报道，青黛鲁宾酮在体外和体内均抑制结直肠癌的生长。青光红酮作为细胞增殖抑制剂的效力与 CRC 细胞中 PAK1 的表达呈负相关。 Glaucarubinone 抑制 HIF-1α 和 β-catenin 的表达。 shRNA 敲低 PAK1 增强了青黛鲁红酮的抑制作用，而组成型活性 PAK1 则阻断了抑制作用。我们的研究结果表明，glaucarubinone 通过 PAK1 依赖性途径下调 HIF-1α 和 β-catenin 来抑制 CRC 生长。
p-21-Activated kinase 1 (PAK1) enhances colorectal cancer (CRC) progression by stimulating Wnt/β-catenin, ERK and AKT pathways. PAK1 also promotes CRC survival via up-regulation of hypoxia-inducible factor 1α (HIF-1α), a key player in cancer survival. Glaucarubinone, a quassinoid natural product, inhibits pancreatic cancer growth by down-regulation of PAK1. The aim of this study was to investigate the effect of glaucarubinone on CRC growth and metastasis, and the mechanism involved. Cell proliferation was measured in vitro by [3H]-thymidine incorporation and in vivo by volume of tumor xenografts. Protein concentrations were measured by Western blotting of cell extracts. We report here that glaucarubinone inhibited CRC growth both in vitro and in vivo. The potency of glaucarubinone as an inhibitor of cell proliferation was negatively correlated to PAK1 expression in CRC cells. Glaucarubinone suppressed the expression of HIF-1α and β-catenin. Knockdown of PAK1 by shRNA enhanced inhibition by glaucarubinone while constitutively active PAK1 blocked the inhibitory effect. Our findings indicate that glaucarubinone inhibited CRC growth by down-regulation of HIF-1α and β-catenin via a PAK1-dependent pathway.
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影响因子：
9.7
作者：
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