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羟基红花黄色素A通过调节Beclin 1和ERK表达诱导人肝癌细胞自噬。

Hydroxysafflor yellow A induces autophagy in human liver cancer cells by regulating Beclin 1 and ERK expression.

作者信息

Chen Ziwei, Liu Li, Liu Yueyun, Wang Shuyan, Zhang Shujing, Dong Ruijuan, Xu Mingyang, Ma Yicong, Wang Jingjing, Zhang Qian, Wei Peng

机构信息

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.

出版信息

Exp Ther Med. 2020 Apr;19(4):2989-2996. doi: 10.3892/etm.2020.8552. Epub 2020 Feb 25.

Abstract

Hydroxysafflor yellow A (HSYA) is a water-soluble component of the safflower (, and research has revealed that HSYA exhibits antitumor effects. In the present study, the effects of HSYA on the autophagy of a Hep-G2 liver cancer cell line, as well as the underlying mechanisms, were investigated. Hep-G2 cells were treated with HSYA and the viability of cells was measured using an MTT assay. Western blotting and immunofluorescence assays were performed to determine the expression of light chain 3 II (LC3-II) and p62, as well as the autophagy regulators Beclin 1 and ERK1/2. Transmission electron microscopy was performed to observe the formation of autophagosomes. The combined effects of HSYA and the autophagy inhibitor chloroquine (CQ) were also determined. The results revealed that the viability of Hep-G2 cells decreased with increasing concentrations of HSYA. Furthermore, LC3-II expression increased significantly and the level of p62 decreased significantly in the HYSA group compared with the control group. Additionally, an increase in Beclin 1 expression and a decrease in phosphorylated-ERK1/2 expression was observed in Hep-G2 cells treated with HYSA. Following treatment with CQ and HSYA, a significant increase in the viability of Hep-G2 cells was observed compared with the HSYA group. Collectively, the results indicated that HSYA induced autophagy by promoting the expression of Beclin 1 and inhibiting the phosphorylation of ERK in liver cancer cells. Therefore, HSYA may serve as a potential therapeutic agent for liver cancer.

摘要

羟基红花黄色素A(HSYA)是红花的一种水溶性成分,研究表明HSYA具有抗肿瘤作用。在本研究中,研究了HSYA对肝癌细胞系Hep-G2自噬的影响及其潜在机制。用HSYA处理Hep-G2细胞,并用MTT法检测细胞活力。进行蛋白质免疫印迹法和免疫荧光分析以确定轻链3 II(LC3-II)和p62的表达,以及自噬调节因子Beclin 1和ERK1/2。进行透射电子显微镜观察自噬体的形成。还确定了HSYA与自噬抑制剂氯喹(CQ)的联合作用。结果显示,随着HSYA浓度的增加,Hep-G2细胞的活力下降。此外,与对照组相比,HSYA组中LC3-II表达显著增加,p62水平显著降低。另外,在用HSYA处理的Hep-G2细胞中观察到Beclin 1表达增加,磷酸化ERK1/2表达降低。用CQ和HSYA处理后,与HSYA组相比,观察到Hep-G2细胞活力显著增加。总体而言,结果表明HSYA通过促进Beclin 1的表达和抑制肝癌细胞中ERK的磷酸化来诱导自噬。因此,HSYA可能作为肝癌的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/7086224/b6a213dc6fcd/etm-19-04-2989-g00.jpg

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