C21 steroid-enriched fraction refined from Marsdenia tenacissima inhibits hepatocellular carcinoma through the coordination of Hippo-Yap and PTEN-PI3K/AKT signaling pathways.
C21 steroid-enriched fraction refined from Marsdenia tenacissima inhibits hepatocellular carcinoma through the coordination of Hippo-Yap and PTEN-PI3K/AKT signaling pathways.
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从 Marsdenia tenacissima 中精制的富含 C21 类固醇的组分通过协调 Hippo-Yap 和 PTEN-PI3K/AKT 信号通路抑制肝细胞癌
DOI：
10.18632/oncotarget.22833
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Zhang Y;Li K;Ying Y;Chen B;Hao K;Chen B;Zheng Y;Lyu J;Tong X;Chen X;Wang Y;Zhan Z;Zhang W;Wang Z
通关藤提取物（MTE）是一种传统的中草药，对多种癌症具有抗肿瘤作用。然而，其在肝细胞癌（HCC）中的有效性和作用机制尚未完全了解。在本研究中，我们证明了C21类固醇富集部分从MTE，其中包含五个主要的C21类固醇（FR 5）在体外和体内对肝癌细胞表现出明显的药理活性。FR 5可诱导HepG 2和Bel 7402细胞凋亡，抑制其增殖和迁移，并呈剂量和时间依赖性。此外，在HCC细胞中，我们发现FR 5抑制Hippo通路，导致雅普失活和PTEN增加。增强的PTEN导致PI 3 K/AKT信号通路的抑制，抑制FR 5引起的细胞增殖和FR 5诱导的细胞凋亡。此外，证明FR 5处理可以抑制肝癌异种移植小鼠模型中的肿瘤生长，并且免疫组织化学结果显示FR 5处理导致Bcl-2和雅普的下调以及PTEN和PI 3 K的上调。综上所述，我们发现FR 5通过协同抑制Hippo通路中的雅普和PI 3 K-PTEN-mTOR通路中的AKT有效地抑制HCC细胞的增殖并诱导其凋亡，并建议FR 5作为HCC的潜在治疗。
Marsdenia tenacissimae extraction (MTE), a traditional herbal medicine, has exhibited anti-tumor effects on a variety of cancers. However, its effectiveness and the mechanism of action in Hepatocellular carcinoma (HCC) has not been fully understood. In the present study, we demonstrate that C21 steroid-enriched fraction from MTE, which contains five main C21 steroids (FR5) exhibits obvious pharmacological activities on HCC cells in vitro and in vivo. FR5 induces apoptosis and inhibits proliferation and migration of HepG2 and Bel7402 cells in a dose and time dependent manner. Furthermore, in HCC cells, we found that FR5 inhibits Hippo pathway, leading to inactivation of YAP and increase of PTEN. Enhanced PTEN results in the inhibition of PI3K/AKT signaling pathway, inhibiting cell proliferation by FR5 and FR5-induced apoptosis. Moreover, it was proved that FR5 treatment could inhibit tumor growth in a HCC xenograft mouse model, and immunohistochemistry results showed FR5 treatment resulted in down-regulation of Bcl-2 and YAP, and up-regulation of PTEN and PI3K. Taken together, we found that FR5 effectively inhibits proliferation and induces apoptosis of HCC cells through coordinated inhibition of YAP in the Hippo pathway and AKT in the PI3K-PTEN-mTOR pathway, and suggest FR5 as a potential therapy for HCC.
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影响因子：
16
作者：
Bhola PD;Letai A
通讯作者：
Letai A
影响因子：
--
作者：
Lynch JT;McEwen R;Crafter C;McDermott U;Garnett MJ;Barry ST;Davies BR
通讯作者：
Davies BR
神经元源性 FGF10 通过抑制 NF-κ B 依赖性神经炎症和激活 PI3K/Akt 存活信号通路改善小鼠脑缺血损伤
影响因子：
4.6
作者：
Li YH;Fu HL;Tian ML;Wang YQ;Chen W;Cai LL;Zhou XH;Yuan HB
通讯作者：
Yuan HB
影响因子：
13.5
作者：
Roayaie, Sasan;Obeidat, Khaled;Sposito, Carlo;Mariani, Luigi;Bhoori, Sherrie;Pellegrinelli, Alessandro;Labow, Daniel;Llovet, Josep M.;Schwartz, Myron;Mazzaferro, Vincenzo
通讯作者：
Mazzaferro, Vincenzo
影响因子：
3.1
作者：
Erasalo, Heikki;Laavola, Mirka;Moilanen, Eeva
通讯作者：
Moilanen, Eeva