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种子油通过 PI3K/AKT/mTOR 信号通路诱导人喉癌细胞自噬和凋亡。

Seed Oil Elicits Autophagy and Apoptosis in Human Laryngeal Tumor Cells via PI3K/AKT/mTOR Signaling Pathway.

机构信息

School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, Shanxi Province, China.

出版信息

Anticancer Agents Med Chem. 2021;21(18):2610-2619. doi: 10.2174/1871520621666210401103820.

DOI:10.2174/1871520621666210401103820
PMID:33797380
Abstract

BACKGROUND

Zanthoxylum bungeanum seed oil (ZBSO) is the main extract of the edible drug Zanthoxylum bungeanum seeds. Recent reports have proved that it has a significant cytotoxic effect on various cancer cells. However, systematic investigation on the role of ZBSO in laryngeal carcinoma (LC) is rare.

OBJECTIVE

The aim of the study was to reveal the function of ZBSO on human laryngeal squamous carcinoma cells (Hep-2) and to elucidate its underlying mechanism.

METHODS

In this study, the chemical composition analysis of ZBSO was done using Ultra Performance Liquid Chromatography (UPLC), and the anti-tumor effect of ZBSO on Hep-2 cells was evaluated by cell proliferation, apoptosis and cell cycle experiments. qRT-PCR, immunohistochemistry (IHC) and Western blotting were used for mechanistic investigation at the molecular level.

RESULTS

The main compound of ZBSO was identified as polyunsaturated fatty acids. Furthermore, as compared to normal cells, significant inhibitory activities of ZBSO were observed on Hep-2 cells with dose- and timedependency, which induced apoptosis, blocked cell cycle at the S phase, and inhibited cell proliferation. In addition, IHC results showed a difference in the level of protein expression of ZBSO-induced autophagy-related markers. At last, Western blotting results indicated that ZBSO could inhibit the expression and phosphorylation levels of PI3K/AKT/mTOR protein.

CONCLUSION

The anti-LC effect of ZBSO might be intimately associated with the induction of autophagy and the inhibition of the PI3K/AKT/mTOR signaling pathway. ZBSO may be a potential anti-laryngocarcinoma agent.

摘要

背景

花椒籽油(ZBSO)是花椒籽食用药物的主要提取物。最近的报道已经证明,它对各种癌细胞具有显著的细胞毒性作用。然而,花椒籽油在喉癌(LC)中的作用的系统研究很少。

目的

本研究旨在揭示 ZBSO 对人喉鳞癌细胞(Hep-2)的作用,并阐明其潜在机制。

方法

本研究采用超高效液相色谱法(UPLC)对 ZBSO 的化学成分进行分析,并通过细胞增殖、凋亡和细胞周期实验评估 ZBSO 对 Hep-2 细胞的抗肿瘤作用。qRT-PCR、免疫组织化学(IHC)和 Western blot 用于在分子水平上进行机制研究。

结果

ZBSO 的主要化合物被鉴定为多不饱和脂肪酸。此外,与正常细胞相比,ZBSO 对 Hep-2 细胞具有明显的剂量和时间依赖性抑制活性,诱导细胞凋亡,阻断细胞周期于 S 期,并抑制细胞增殖。此外,IHC 结果显示 ZBSO 诱导的自噬相关标志物的蛋白表达水平存在差异。最后,Western blot 结果表明 ZBSO 可以抑制 PI3K/AKT/mTOR 蛋白的表达和磷酸化水平。

结论

ZBSO 的抗 LC 作用可能与诱导自噬和抑制 PI3K/AKT/mTOR 信号通路密切相关。ZBSO 可能是一种有潜力的抗喉癌药物。

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