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牛磺酸对人肺癌A549细胞增殖和凋亡的影响。

Effect of taurine on cell proliferation and apoptosis human lung cancer A549 cells.

作者信息

Tu Shuo, Zhang Xia-Li, Wan Hui-Fang, Xia Yan-Qin, Liu Zhuo-Qi, Yang Xiao-Hong, Wan Fu-Sheng

机构信息

Department of Biochemistry and Molecular Biology, Basic Medical College of Nan Chang University, Nanchang, Jiangxi 330006, P.R. China.

Department of Laboratory Animal Science, Nan Chang University, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):5473-5480. doi: 10.3892/ol.2018.8036. Epub 2018 Feb 13.

Abstract

To investigate the effects of taurine on cell proliferation and apoptosis, the human lung cancer A549 cell line and xenograft tumors in nude mice were used. The effects of taurine on cell proliferation and apoptosis were observed at time points of 24, 48 and 72 h after treatment using an MTT assay to detect the survival rate, and flow cytometry to detect the apoptotic rate. Western blot analysis was performed to examine the levels of p53 upregulated modulator of apoptosis (PUMA), BCL2, apoptosis regulator (Bcl-2) and BCL2-associated X, apoptosis regulator (Bax) in A549 cells. The level of PUMA, Bax and Bcl-2 proteins in the mouse xenograft tumors treated with taurine and/or exogenous PUMA were assessed by immunohistochemistry, with taurine suppressing the proliferation of the human lung cancer A549 cell line in a concentration-dependent manner, and it significantly enhanced the apoptosis rate at all concentrations. Taurine induced the significant upregulation of PUMA and Bax, but led to downregulation of Bcl-2. In comparison to the control group, taurine treatment markedly reduced the volume and weight of A549-derived xenograft tumors in nude mice. Expression of PUMA and Bax were upregulated in the xenograft tumors following taurine treatment, whereas Bcl-2 was downregulated. In addition, the inhibitory effect of taurine and exogenous PUMA on tumor growth was significantly higher than that of a single treatment of taurine or exogenous PUMA. It can therefore be concluded that taurine can inhibit cell proliferation of the human lung cancer A549 cell line and the growth of the xenograft tumors, whereas PUMA serves an important role in taurine-induced growth suppression.

摘要

为研究牛磺酸对细胞增殖和凋亡的影响,使用了人肺癌A549细胞系和裸鼠异种移植瘤。在处理后的24、48和72小时时间点,采用MTT法检测存活率以观察牛磺酸对细胞增殖的影响,采用流式细胞术检测凋亡率以观察其对细胞凋亡的影响。进行蛋白质免疫印迹分析以检测A549细胞中凋亡调节蛋白p53上调调节因子(PUMA)、B细胞淋巴瘤/白血病-2(BCL2)、凋亡调节蛋白(Bcl-2)和BCL2相关X蛋白、凋亡调节蛋白(Bax)的水平。通过免疫组织化学评估用牛磺酸和/或外源性PUMA处理的小鼠异种移植瘤中PUMA、Bax和Bcl-2蛋白的水平,牛磺酸以浓度依赖性方式抑制人肺癌A549细胞系的增殖,并且在所有浓度下均显著提高凋亡率。牛磺酸诱导PUMA和Bax显著上调,但导致Bcl-2下调。与对照组相比,牛磺酸处理显著降低了裸鼠中A549来源的异种移植瘤的体积和重量。牛磺酸处理后,异种移植瘤中PUMA和Bax的表达上调,而Bcl-2下调。此外,牛磺酸和外源性PUMA对肿瘤生长的抑制作用明显高于单独使用牛磺酸或外源性PUMA的处理。因此可以得出结论,牛磺酸可抑制人肺癌A549细胞系的细胞增殖和异种移植瘤的生长,而PUMA在牛磺酸诱导的生长抑制中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5bc/5840730/a7e6ea58c9ce/ol-15-04-5473-g00.jpg

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