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苦参碱通过调控上皮-间质转化抑制人肝癌细胞的侵袭和迁移能力。

Matrine inhibits the invasive and migratory properties of human hepatocellular carcinoma by regulating epithelial‑mesenchymal transition.

机构信息

Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, P.R. China.

Department of Pathology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Mol Med Rep. 2018 Jul;18(1):911-919. doi: 10.3892/mmr.2018.9023. Epub 2018 May 16.

Abstract

Matrine has been reported to be an effective anti‑tumor therapy; however, the anti-metastatic effects of matrine on hepatocellular carcinoma (HCC) and the molecular mechanism(s) involved remain unclear. Therefore, the aims of the present study were to evaluate the effects of matrine on hepatoma and to determine the associated mechanism(s) involved. In the present study, matrine was confirmed to prevent the proliferation of HCC cells and it was observed that matrine also inhibited the migratory, and invasive capabilities of HCC at non‑toxic concentrations. Additionally, matrine increased epithelial‑cadherin expression and decreased the expression levels of vimentin, matrix metalloproteinase (MMP)2, MMP9, zinc finger protein SNAI1 and zinc finger protein SNAI2. These results indicate that the anti‑metastatic effect of matrine may be associated with epithelial‑mesenchymal transition (EMT). Furthermore, matrine can increase phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN (PTEN) expression and reduce phosphorylated‑protein kinase B (Akt) levels. In conclusion, these results suggested that matrine is a potential therapeutic agent that can suppress cancer‑associated invasion and migration via PTEN/Akt‑dependent inhibition of EMT.

摘要

苦参碱已被报道为一种有效的抗肿瘤治疗药物;然而,苦参碱对肝癌的抗转移作用及其涉及的分子机制尚不清楚。因此,本研究旨在评估苦参碱对肝癌的作用,并确定相关的作用机制。在本研究中,苦参碱被证实可预防肝癌细胞的增殖,并且还观察到苦参碱在非毒性浓度下也抑制肝癌细胞的迁移和侵袭能力。此外,苦参碱增加了上皮钙黏蛋白的表达,降低了波形蛋白、基质金属蛋白酶(MMP)2、MMP9、锌指蛋白 SNAI1 和锌指蛋白 SNAI2 的表达水平。这些结果表明,苦参碱的抗转移作用可能与上皮-间充质转化(EMT)有关。此外,苦参碱可以增加磷脂酰肌醇 3,4,5-三磷酸 3-磷酸酶和双特异性蛋白磷酸酶 PTEN(PTEN)的表达,并降低磷酸化蛋白激酶 B(Akt)的水平。总之,这些结果表明,苦参碱是一种潜在的治疗药物,可通过 PTEN/Akt 依赖性抑制 EMT 来抑制与癌症相关的侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdd2/6059723/79cfceb0566f/MMR-18-01-0911-g00.jpg

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