Astragaloside IV suppresses migration and invasion of TGF-β1-induced human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-β1/Smad3 pathways
Astragaloside IV suppresses migration and invasion of TGF-β1-induced human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-β1/Smad3 pathways
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黄芪甲苷 IV 通过调节 Nrf2/HO-1 和 TGF-β1/Smad3 途径抑制 TGF-β1 诱导的人肝癌 HuH-7 细胞的迁移和侵袭
DOI：
10.1007/s00210-021-02199-8
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Pang Xiaonan
中科院分区：
文献类型：
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作者：
Li Lili;Wang Qin;He Yinghao;Sun Liangjie;Yang Yan;Pang Xiaonan
黄芪甲苷（AS-IV）是黄芪的主要有效成分之一，对多种恶性肿瘤有较好的抗肿瘤作用。氧化应激（OS）被认为是促进肝细胞癌（HCC）进展的关键因素。作为对OS的响应，核因子红细胞2相关因子2（Nrf 2）上调并诱导血红素加氧酶1（HO-1）以对抗氧化损伤。Smad 3羧基端的磷酸化（pSmad 3C）激活p21以抵抗HCC的进展，而Smad 3连接区的磷酸化（pSmad 3L）上调c-Myc的转录以发挥对HCC的促进作用。本研究旨在探讨AS-IV是否通过调节Nrf 2/HO-1和TGF-β1/Smad 3通路抑制人肝癌HuH-7细胞的迁移和侵袭。用TGF-β1（9或40 pM）诱导HuH-7细胞建立肝癌细胞模型，用不同浓度（5、10和20 μM）的AS-IV预处理24 h。测定细胞增殖、迁移、侵袭和细胞内活性氧（ROS）。检测Nrf 2、pSmad 3C、Nrf 2/pNrf 2、HO-1、pSmad 3C/3L、c-Myc和p21的表达。TGF-β 1可促进HuH-7细胞的增殖、迁移、侵袭和活性氧的产生。用AS-IV（5、10和20 μM）预处理显著降低HuH-7细胞的细胞增殖、迁移、侵袭和ROS产生。AS-IV还可上调Nrf 2/pNrf 2、HO-1、pSmad 3C和p21的表达，下调pSmad 3L和c-Myc的表达。结论：AS-Ⅳ抑制HuH-7细胞的迁移和侵袭，其机制可能与激活Nrf 2/HO-1通路，上调pSmad 3C/p21通路，下调pSmad 3L/c-Myc通路有关。目前的研究支持的概念，AS-IV可能是一个潜在的代理人治疗肝癌。
Astragaloside IV (AS-IV), one of the major compounds extract from Astragalus membranaceus, has shown attractive anti-cancer effects in certain malignancies. Oxidative stress (OS) is considered as a crucial factor in promoting the progression of hepatocellular carcinoma (HCC). In response to OS, nuclear factor erythroid 2-related factor 2 (Nrf2) upregulates and induces heme oxygenase 1 (HO-1) to combat oxidative damages. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) activates p21 to resist HCC progression, while the phosphorylation of the linker region of Smad3 (pSmad3L) up-regulates c-Myc transcription to exert promoting effect towards HCC. This study aimed to explore whether AS-IV suppresses migration and invasion of human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-β1/Smad3 pathways. HuH-7 cells were induced with TGF-β1(9 or 40 pM) to establish HCC model in vitro and pretreated with AS-IV at different concentration (5, 10, and 20 μM) for 24 h. Cell proliferation, migration, invasion, and intracellular reactive oxygen species (ROS) of HuH-7 cells were measured. The expression of Nrf2, pSmad3C, Nrf2/pNrf2, HO-1, pSmad3C/3L, c-Myc, and p21 were detected. Exposure of HuH-7 cells to TGF-β1enhanced the cell proliferation, migration, invasion, and ROS production. Pretreatment with AS-IV (5, 10, and 20 μM) significantly reduced the cell proliferation, migration, invasion, and ROS production in HuH-7 cells. Furthermore, AS-IV increased the expressions of Nrf2/pNrf2, HO-1, pSmad3C, and p21, meanwhile reduced the expressions of pSmad3L and c-Myc. In conclusion, our study suggested that AS-IV inhibit HuH-7 cells migration and invasion, which related to activate Nrf2/HO-1 pathway, up-regulation pSmad3C/p21 pathway, and down-regulation pSmad3L/c-Myc pathway. The present research supports the notion that AS-IV may be a latent agent for the treatment of HCC.
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CUL4B、NEDD4 和 UGT1As 参与肝细胞癌中的 TGF-β 信号转导。
影响因子：
3.8
作者：
Zhaowei Qu;Di Li;Haitao Xu;Rujia Zhang;Bing Li;Chengming Sun;W. Dong;Yubao Zhang
通讯作者：
Yubao Zhang
黄芪甲苷 IV 通过 AMPK 信号传导调节巨噬细胞极化来抑制肺癌进展和转移。
DOI：
10.1186/s13046-018-0878-0
发表时间：
2018-08-29
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Xu F;Cui WQ;Wei Y;Cui J;Qiu J;Hu LL;Gong WY;Dong JC;Liu BJ
通讯作者：
Liu BJ
影响因子：
4.3
作者：
Takashi Yamaguchi;Katsunori Yoshida;M. Murata;K. Matsuzaki
通讯作者：
Takashi Yamaguchi;Katsunori Yoshida;M. Murata;K. Matsuzaki
影响因子：
7.5
作者：
Li, Yaling;Ye, Yun;Chen, Hongyan
通讯作者：
Chen, Hongyan
星形镜IV通过激活NRF2信号途径来减轻小鼠乙酰氨基酚诱导的肝损伤。
DOI：
10.3390/molecules23082032
发表时间：
2018-08-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Li L;Huang W;Wang S;Sun K;Zhang W;Ding Y;Zhang L;Tumen B;Ji L;Liu C
通讯作者：
Liu C