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莴苣苦素在SKMEL-5人皮肤癌细胞中的抗癌作用是通过诱导凋亡、使G2/M期细胞周期停滞以及下调mTOR/PI3K/AKT信号通路来介导的。

Anticancer action of lactucopicrin in SKMEL-5 human skin cancer cells is mediated via apoptosis induction, G2/M cell cycle arrest and downregulation of m=TOR/PI3K/AKT signalling pathway.

作者信息

Zhang Xue, Lan Dong, Ning Shuhua, Ruan Liwen

机构信息

Department of Dermatology and Plastic Surgery, Beijing Chaoyang Hospital, Jingxi Xijing Campus, Capital Medical University, Beijing, China.

出版信息

J BUON. 2018 Jan-Feb;23(1):224-228.

Abstract

PURPOSE

Skin cancer is one of the cancers responsible for significant morbidity and mortality across the globe. The treatment options for skin cancer are limited and associated with significant toxicity. Therefore, researches have been directed towards exploring molecules that could prove beneficial in the treatment of this disease. Lactucopicrin is an important sesquiterpene lactone with important pharmacological potential.

METHODS

In the present study the anticancer effects of lactucopicrin against human skin SKMEL-5 cancer cell line were investigated. Antiproliferative effects were examined by CCK-8 assay. Apoptosis was detected by DAPI and annexin V/propidium iodide (PI) staining. Cell cycle analysis was carried out by flow cytometry. Protein expression was determined by western blotting.

RESULTS

The results indicated that lactucopicrin exerts significant anticancer effects on the SKMEL-5 cells with an IC50 of 7.5 μM. Its anticancer effects were due to induction of apoptosis. Lactucopicrin could upregulate the expression of Bax which was associated with concomitant downregulation of Bcl-2 expression. Additionally, lactucopicrin induced G2/M cell cycle arrest in SKMEL-5 cells in a dose-dependent manner and also inhibited the m-TOR/PI3K/AKT signalling pathway.

CONCLUSION

These results indicate that lactucopicrin shows potent anticancer action in the tested skin cancer cells and may prove a prospective lead molecule for the treatment of skin cancer.

摘要

目的

皮肤癌是全球范围内导致显著发病率和死亡率的癌症之一。皮肤癌的治疗选择有限且伴有显著毒性。因此,研究一直致力于探索可能对治疗这种疾病有益的分子。莴苣苦素是一种具有重要药理潜力的重要倍半萜内酯。

方法

在本研究中,研究了莴苣苦素对人皮肤SKMEL - 5癌细胞系的抗癌作用。通过CCK - 8测定法检测抗增殖作用。通过DAPI和膜联蛋白V/碘化丙啶(PI)染色检测细胞凋亡。通过流式细胞术进行细胞周期分析。通过蛋白质印迹法测定蛋白质表达。

结果

结果表明,莴苣苦素对SKMEL - 5细胞具有显著的抗癌作用,IC50为7.5 μM。其抗癌作用归因于诱导细胞凋亡。莴苣苦素可上调Bax的表达,这与Bcl - 2表达的同时下调相关。此外,莴苣苦素以剂量依赖性方式诱导SKMEL - 5细胞的G2/M期细胞周期阻滞,并且还抑制m - TOR/PI3K/AKT信号通路。

结论

这些结果表明,莴苣苦素在测试的皮肤癌细胞中显示出强大的抗癌作用,可能成为治疗皮肤癌的一种有前景的先导分子。

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