Abstract

Context

Myristicin is a natural active compound that has inflammatory, antimicrobial and anti-proliferative properties. Yet, its effect on hepatic carcinoma has not been investigated.

Objective

To explore the role and related molecular mechanism of myristicin in hepatic carcinoma in vitro.

Materials and methods

Human hepatic carcinoma cell lines (Huh-7 and HCCLM3 cells) were treated with different concentrations of myristicin (0.5, 1 and 5 mM) for 24, 48 and 72 h. Then, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay (MTT), flow cytometer (FCM) analysis and transwell assay were performed to determine cell proliferation, apoptosis and migration/invasion, respectively. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), E-cadherin, N-cadherin and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway-related proteins were detected using Western blot assay. Gene expression was determined using quantitative real time-polymerase chain reaction (qRT-PCR).

Results

Myristicin inhibited cell proliferation and induced apoptosis in Huh-7 and HCCLM3 cells; suppressed cell migration and invasion ability, and increased E-cadherin expression and decreased N-cadherin expression, thereby inhibiting epithelial–mesenchymal transition (EMT). Finally, the findings indicated that myristicin decreased phosphorylated (p)-mTOR and p-AKT expression at the protein level.

Discussion and conclusions

Myristicin exerts an efficient therapeutic effect on hepatic carcinoma by suppressing PI3K/Akt/mTOR signalling pathway; thus, it may be used as a new potential drug for hepatic carcinoma treatment.

中文翻译：

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肉豆蔻碱对肝癌的抗癌作用及相关分子机制

摘要

语境

肉豆蔻素是一种具有抗炎、抗菌和抗增殖特性的天然活性化合物。然而，尚未研究其对肝癌的影响。

客观的

探讨肉豆蔻碱在体外肝癌中的作用及相关分子机制。

材料和方法

人肝癌细胞系（Huh-7 和 HCCLM3 细胞）用不同浓度的肉豆蔻素（0.5、1 和 5 mM）处理 24、48 和 72 小时。然后，进行 (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) 四唑测定 (MTT)、流式细胞仪 (FCM) 分析和 transwell 测定以测定细胞增殖、凋亡和迁移/分别入侵。B 细胞淋巴瘤 2 (Bcl-2)、Bcl-2 相关 X (Bax)、E-钙粘蛋白、N-钙粘蛋白和磷脂酰肌醇 3-激酶 (PI3K)/蛋白激酶 B (AKT)/哺乳动物靶点的蛋白质水平使用蛋白质印迹法检测雷帕霉素（mTOR）信号通路相关蛋白。使用定量实时聚合酶链式反应（qRT-PCR）确定基因表达。

结果

肉豆蔻素在 Huh-7 和 HCCLM3 细胞中抑制细胞增殖并诱导细胞凋亡；抑制细胞迁移和侵袭能力，增加 E-cadherin 表达和降低 N-cadherin 表达，从而抑制上皮-间质转化（EMT）。最后，研究结果表明肉豆蔻素降低了蛋白质水平的磷酸化 (p)-mTOR 和 p-AKT 表达。

讨论和结论

肉豆蔻素通过抑制PI3K/Akt/mTOR信号通路发挥有效治疗肝癌的作用；因此，它可能被用作治疗肝癌的新的潜在药物。