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下调的miR-21通过PTEN/Akt信号通路介导苦参碱诱导的FTC-133人甲状腺滤泡癌细胞凋亡。

Downregulated miR-21 mediates matrine-induced apoptosis via the PTEN/Akt signaling pathway in FTC-133 human follicular thyroid cancer cells.

作者信息

Li Quanliang, Zhang Shuya, Wang Mingyu, Dong Shouguang, Wang Yan, Liu Song, Lu Tiancheng, Fu Yuqin, Wang Xiuran, Chen Guihong

机构信息

Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, College of Life Sciences, Jilin Agricultural University, Changchun, Jilin 130118, P.R. China.

Jilin Hongwuwei BioTech Company, Ji'an, Jilin 134200, P.R. China.

出版信息

Oncol Lett. 2019 Oct;18(4):3553-3560. doi: 10.3892/ol.2019.10693. Epub 2019 Jul 31.

Abstract

Matrine is an alkaloid extracted from the leguminous plant . Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC-133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC-133 cells in a dose- and time-dependent manner with an IC value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC-133 cells. The expression level of microRNA (miR)-21 was analyzed by reverse transcription-quantitative PCR (RT-qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)-Akt were detected by RT-qPCR analysis and western blotting, respectively. The expression of miR-21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p-Akt was downregulated in the FTC-133 cells. The effects of miR-21 mimics and miR-21 inhibitor on the expression of miR-21, PTEN and Akt in FTC-133 cells, and the effect of miR-21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC-133 cells via the miR-21/PTEN/Akt signaling pathway.

摘要

苦参碱是从豆科植物中提取的一种生物碱。苦参碱在肿瘤治疗中具有临床疗效,包括肺癌、鼻咽癌和肝癌等。然而,苦参碱对滤泡状甲状腺癌的作用尚未见报道。本研究的目的是探讨苦参碱对滤泡状甲状腺癌的作用及其潜在机制。用不同浓度的苦参碱处理FTC-133滤泡状甲状腺癌细胞,MTT法检测结果显示,苦参碱以剂量和时间依赖性方式抑制FTC-133细胞的生长,IC值为154.8µM。通过流式细胞术分析细胞凋亡,结果表明苦参碱可有效诱导FTC-133细胞凋亡。通过逆转录定量PCR(RT-qPCR)分析检测微小RNA(miR)-21的表达水平,分别通过RT-qPCR分析和蛋白质印迹法检测PTEN、Akt和磷酸化(p)-Akt的mRNA和蛋白质表达水平。在FTC-133细胞中,miR-21的表达显著下调,PTEN在mRNA和蛋白质表达水平上上调,p-Akt下调。还研究了miR-21模拟物和miR-21抑制剂对FTC-133细胞中miR-21、PTEN和Akt表达的影响,以及miR-21模拟物/苦参碱对PTEN表达的影响。本研究结果表明,苦参碱通过miR-21/PTEN/Akt信号通路抑制FTC-133细胞的生长并诱导其凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/6757298/0026ed92823e/ol-18-04-3553-g00.jpg

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