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软枣猕猴桃根提取物通过抑制上皮-间充质转化来抑制肝癌的增殖和转移。

Actinidia chinensis Planch root extract attenuates proliferation and metastasis of hepatocellular carcinoma by inhibiting epithelial-mesenchymal transition.

机构信息

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China.

Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China.

出版信息

J Ethnopharmacol. 2019 Mar 1;231:474-485. doi: 10.1016/j.jep.2018.11.014. Epub 2018 Nov 8.

Abstract

ETHNO-PHARMACOLOGICAL RELEVANCE: Numerous studies have demonstrated the potent anticancer activity of various Chinese herbs. Actinidia chinensis Planch root (acRoots), a traditional Chinese medicine, functions as an antitumor and detoxifying agent and plays a role in diuresis and hemostasis. Treatment with acRoots confers strong inhibition of tumor growth in various forms of cancer. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC).

MATERIALS AND METHODS

Our previous study used mRNA chip analyses to identify the genes regulated by acRoots. Further analyses of the altered genes identified a key regulator of genes in response to acRoots. Here, the effects of acRoots on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by cell counting, Transwell and apoptosis assays. In addition, the in vivo anti-HCC effects of acRoots were investigated using an HCC animal model. The expression of a key regulator of genes in response to acRoots was analyzed using quantitative polymerase chain reaction and western blotting.

RESULTS

Treatment with acRoots (10 mg/mL) had no cytotoxicity in L02 cells and had a positive effect on L02 cell viability; however, it significantly inhibited HCC cell proliferation. Treatment with acRoots downregulated DLX2 gene expression in HCC cells, and high DLX2 expression was associated with advanced stage and poor prognosis in patients with HCC. Treatment with acRoots inhibited proliferation, invasion and migration, clonality, and the epithelial-to-mesenchymal transition, and promoted the apoptosis of HCC cells by downregulating DLX2 expression. HCC cells with higher DLX2 expression were more sensitive to acRoots.

CONCLUSIONS

acRoots inhibited the malignant biological behavior of HCC cells via regulation of the epithelial-mesenchymal transition (EMT) by DLX2.

摘要

民族药理学相关性

多项研究表明,各种中药具有很强的抗癌活性。猕猴桃根(acRoots)是一种传统中药,具有抗肿瘤、解毒作用,并有利尿、止血作用。acRoots 的治疗对各种形式的癌症具有很强的抑制肿瘤生长作用。在这里,我们评估了猕猴桃根提取物(acRoots)对肝细胞癌(HCC)的抗癌活性和分子机制。

材料和方法

我们之前的研究使用 mRNA 芯片分析来鉴定受 acRoots 调节的基因。对改变的基因的进一步分析确定了对 acRoots 反应的基因的关键调节剂。在这里,通过细胞计数、Transwell 和凋亡测定评估 acRoots 对 HCC 细胞增殖、迁移、侵袭和凋亡的影响。此外,使用 HCC 动物模型研究了 acRoots 的体内抗 HCC 作用。使用定量聚合酶链反应和蛋白质印迹分析鉴定响应 acRoots 的基因的关键调节剂的表达。

结果

acRoots(10mg/ml)处理对 L02 细胞没有细胞毒性,对 L02 细胞活力有积极影响,但明显抑制 HCC 细胞增殖。acRoots 处理下调 HCC 细胞中 DLX2 基因表达,高 DLX2 表达与 HCC 患者的晚期和预后不良相关。acRoots 处理通过下调 DLX2 表达抑制 HCC 细胞增殖、侵袭和迁移、克隆形成和上皮-间充质转化,并促进 HCC 细胞凋亡。具有较高 DLX2 表达的 HCC 细胞对 acRoots 更敏感。

结论

acRoots 通过调节 EMT 中的 DLX2 抑制 HCC 细胞的恶性生物学行为。

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