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首页> 外文期刊>RSC Advances >Sinomenine inhibits ovarian cancer cell growth and metastasis by mediating the Wnt/beta-catenin pathway via targeting MCM2
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Sinomenine inhibits ovarian cancer cell growth and metastasis by mediating the Wnt/beta-catenin pathway via targeting MCM2

机译：通过鉴定MCM2介导WNT /β-连环蛋白途径，Sinomenine抑制卵巢癌细胞生长和转移

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摘要

Sinomenine (SIN), an isoquinoline isolated from the Chinese medicinal plant Sinomenium acutum, is well known for its curative effect on rheumatic and arthritic diseases. Recently, SIN has been reported to possess potent anti-tumor effects in various types of cancers. However, the role and the underlying mechanism of the inhibitory action of SIN on ovarian cancer remain unknown. In this study, we preliminarily found that SIN might suppress tumor proliferation and metastasis by modulating the oncogene MCM2 and the Wnt/beta-catenin signaling pathway. The results demonstrated that SIN could inhibit ovarian cancer cell proliferation in a dose-dependent manner. IGROV1 or HeyA8 cells treated with 0.25 mM, 0.5 mM, and 1 mM SIN exhibited gradually reduced growth capacity. Correspondingly, the protein expression levels of c-myc and cyclinD1 were also obviously decreased. In addition, reduction in migration and invasion rates was found in IGROV1 or HeyA8 cells treated with 0.25 mM and 0.5 mM SIN. Western blot results revealed that SIN could upregulate the protein expression levels of epithelial markers such as ZO-1 and E-cadherin; it also downregulated the protein expression levels of mesenchymal markers, i.e., vimentin, N-cadherin, ZEB1, and Snail. Furthermore, Wnt/beta-catenin signaling attenuation was followed by the suppression of total beta-catenin, cytoplasmic beta-catenin, and nuclear beta-catenin due to SIN treatment. MCM2 was verified to exhibit a positive relation with ovarian cancer malignancy in 75 ovarian cancer tissue and 15 paracancer tissue samples. Furthermore, MCM2 could be reduced by SIN, and its overexpression could rescue the loss of beta-catenin, ZEB1, c-myc, and cyclinD1 mRNA levels together with beta-catenin and ZEB1 protein expression levels, which could markedly be inhibited by MCM2 knockdown again. In summary, SIN might play anti-proliferation and anti-metastasis functions in ovarian cancer via targeting MCM2 and thereby regulating the Wnt/beta-catenin signaling pathway. Thus, it could be considered to be a promising chemopreventive compound to treat ovarian carcinoma.
机译：SINOMENINE（SIN）是从中药植物中胚菌中分离的异喹啉，以其对风湿和关节炎疾病的疗效而闻名。最近，据报道，罪恶已经在各种类型的癌症中具有有效的抗肿瘤作用。然而，罪恶对卵巢癌的抑制作用的作用和潜在机制仍然未知。在这项研究中，我们初步发现，通过调节癌基因MCM2和WNT /β-连环蛋白信号传导途径来抑制犯罪抑制肿瘤增殖和转移。结果表明，SIN以剂量依赖性方式抑制卵巢癌细胞增殖。用0.25mm，0.5mm和1mm in处理的Igrov1或Heya8细胞表现出逐渐降低生长能力。相应地，C-MYC和CYCLIND1的蛋白质表达水平也明显降低。此外，在用0.25mm和0.5mm的IGROV1或Heya8细胞中发现迁移和侵袭率的降低。 Western印迹结果表明，SIN可以上调上皮标志物的蛋白质表达水平，例如ZO-1和E-Cadherin;它还下调了间充质标志物的蛋白质表达水平，即，Vimentin，N-Cadherin，Zeb1和蜗牛。此外，由于SIN治疗，WNT /β-catenin信号传导衰减随后抑制了总β-连环蛋白，细胞质β-连环蛋白和核β-连环蛋白。核实MCM2在75个卵巢癌组织和15个副副癌组织样品中表现出与卵巢癌恶性肿瘤的阳性关系。此外，MCM2可以通过SIN降低，其过表达可以拯救与β-catenin和Zeb1蛋白表达水平一起拯救β-catenin，Zeb1，C-myc和Cyclind1 mRNA水平的丧失，这可以明显被MCM2敲低抑制再次。总之，SIN可能通过靶向MCM2在卵巢癌中发挥抗扩散和抗转移功能，从而调节WNT /β-连环蛋白信号传导途径。因此，可以认为是一种有前途的化学预防化合物，以治疗卵巢癌。

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  • 来源
    《RSC Advances》 |2017年第79期|共10页
  • 作者

    Li Huimin; Lin Zhikun; Bai Yuxin; Chi Xinming; Fu Hailu; Sun Rui; Liu Meizi; Liu Xuan; Chen Liying; Shao Shujuan;

  • 作者单位

    Dalian Med Univ Dept Histol &

    Embryol Dalian 116044 Peoples R China;

    Dalian Med Univ Affiliated Hosp 1 Dalian 116011 Peoples R China;

    Dalian Med Univ Dept Histol &

    Embryol Dalian 116044 Peoples R China;

    Dalian Med Univ Key Lab Prote Dalian 116044 Peoples R China;

    Dalian Med Univ Dept Histol &

    Embryol Dalian 116044 Peoples R China;

    Dalian Med Univ Affiliated Hosp 2 Dalian 116023 Peoples R China;

    Dalian Med Univ Affiliated Hosp 1 Dalian 116011 Peoples R China;

    Dalian Med Univ Dept Histol &

    Embryol Dalian 116044 Peoples R China;

    Dalian Med Univ Dept Histol &

    Embryol Dalian 116044 Peoples R China;

    Dalian Med Univ Key Lab Prote Dalian 116044 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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