Huaier aqueous extract inhibits ovarian cancer cell motility via the AKT/GSK3β/β-catenin pathway.
Huaier aqueous extract inhibits ovarian cancer cell motility via the AKT/GSK3β/β-catenin pathway.
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DOI：
10.1371/journal.pone.0063731
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Feng W
中科院分区：
文献类型：
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作者：
Yan X;Lyu T;Jia N;Yu Y;Hua K;Feng W
传统中药因其杀死肿瘤细胞的能力而受到欢迎。近年来，槐耳栓菌穆尔（Trametes robiniophila（Huaier））的抗血管生成作用和凋亡作用被广泛研究。本研究的目的是研究其对卵巢癌细胞运动和肿瘤生长的影响。使用SRB、划痕和迁移测定来测量细胞活力和运动性。Annexin V/PI染色检测细胞凋亡。使用反相蛋白质阵列（RPPA）分析，我们分析了怀尔处理和未处理细胞中153种蛋白质和/或磷酸化的水平。槐耳液对SKOV 3、SKOV3.ip1和Hey细胞的存活率有抑制作用，并以时间和剂量依赖性方式诱导早期和晚期凋亡。细胞的侵袭和迁移也被显著抑制。RPPA结果显示未处理和处理细胞之间SKOV 3细胞中7种分子和SKOV3.ip1细胞中10种分子的水平存在显著差异（至少30%; P <0.05）。大多数鉴定的分子在细胞增殖、凋亡或细胞粘附/侵袭中起作用。Western blot分析进一步证实，怀尔处理导致AKT磷酸化降低，总GSK 3 β表达增强，抑制GSK 3 β在S9上的磷酸化，细胞质β-catenin表达和细胞核β-catenin易位减少，以及几个Wnt/β-catenin靶基因（DIXDC 1，LRP 6，WNT 5A和cyclin D1）的转录抑制。在敲低GSK 3 β后，槐耳不能抑制β-catenin的表达。最后，槐耳在体内抑制卵巢肿瘤异种移植物的生长。这些研究表明，怀尔通过AKT/GSK 3 β/β-catenin信号通路抑制卵巢癌中的肿瘤细胞移动。
Traditional Chinese medicine has gained popularity due to its ability to kill tumor cells. Recently, the apoptotic and anti-angiogenic effects of Trametes robiniophila murr (Huaier) have been investigated. The aim of this study was to investigate its effect on cell mobility and tumor growth in ovarian cancer. Cell viability and motility were measured using SRB, scratch and migration assays. Cell apoptosis was analysed by annexin V/PI staining. Using a reverse-phase protein array (RPPA) assay, we analyzed the levels of 153 proteins and/or phosphorylations in Huaier-treated and untreated cells. Huaier inhibited cell viability and induced both early and late apoptosis in SKOV3, SKOV3.ip1 and Hey cells in a time- and dose-dependent manner. Cell invasiveness and migration were also suppressed significantly. The RPPA results showed significant differences (of at least 30%; P <0.05) in the levels of 7 molecules in SKOV3 cells and 10 in SKOV3.ip1 cells between the untreated and treated cells. Most of the molecules identified play roles in cell proliferation, apoptosis or cell adhesion/invasion. Western blot analysis further validated that Huaier treatment resulted in decreased AKT phosphorylation, enhanced expression of total GSK3β, inhibition of the phosphorylation of GSK3β on S9, reduction of both cytoplasmic β-catenin expression and nuclear β-catenin translocation, and transcriptional repression of several Wnt/β-catenin target genes (DIXDC1, LRP6, WNT5A, and cyclin D1). After knocking down GSK3β, β-catenin expression could not be inhibited by Huaier. Finally, Huaier inhibited the growth of ovarian tumor xenografts in vivo. These studies indicate that Huaier inhibits tumor cell mobility in ovarian cancer via the AKT/GSK3β/β-catenin signaling pathway.
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影响因子：
11.2
作者：
Onder, Tamer T.;Gupta, Piyush B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
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影响因子：
3.7
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He Y;Zhou Z;Hofstetter WL;Zhou Y;Hu W;Guo C;Wang L;Guo W;Pataer A;Correa AM;Lu Y;Wang J;Diao L;Byers LA;Wistuba II;Roth JA;Swisher SG;Heymach JV;Fang B
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Fang B
影响因子：
5.7
作者：
Tibes, Raoul;Qiu, YiHua;Kornblau, Steven M.
通讯作者：
Kornblau, Steven M.
影响因子：
158.5
作者：
Burger, Robert A.;Brady, Mark F.;Liang, Sharon X.
通讯作者：
Liang, Sharon X.
影响因子：
8.8
作者：
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