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三氧化二砷通过下调细胞外基质和p27的表达来抑制视网膜色素上皮细胞的增殖。

Arsenic trioxide inhibits proliferation of retinal pigment epithelium by downregulating expression of extracellular matrix and p27.

作者信息

Su Ying, Wang Feng, Hu Qi, Qu Yixin, Han Ying

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University Harbin, China.

Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University Harbin, China.

出版信息

Int J Clin Exp Pathol. 2020 Feb 1;13(2):172-178. eCollection 2020.

Abstract

The present study aimed to investigate the effect of arsenic trioxide (ATO) on the proliferation of retinal pigment epithelium (RPE) and its mechanism. RPE cells were cultivated with 0.5-11 μmol/L ATO for 24, 48, and 72 h and their survival and growth were measured by MTT assay. The expression of p27 and proliferating cell nuclear antigen (PCNA) in RPE cells was detected using cell immunofluorescence and western blotting. Dose-dependency was evident in both the experimental and control groups. The 50% inhibitory concentration was obtained at a concentration of 6 mol/L with cells treated for 3 days. The optimum concentration of ATO was 6 μmol/L based on the result of MTT. After the third day of ATO treatment, the number of cells was significantly lower in the experimental group compared with the control group. The expression of extracellular matrix (ECM) components decreased relative to the control group. The expression of p27 and PCNA declined gradually in cells treated for 72 h at 6 μmol/L ATO compared with the control group. The difference between the experimental and control groups was significant (). ATO has the ability to inhibit the growth and proliferation of RPE cells by regulating the expression of the ECM components' p27 and PCNA, in a time- and dose-dependent manner. Thus, ATO may lead to an innovative method for the treatment of proliferative retinopathy.

摘要

本研究旨在探讨三氧化二砷(ATO)对视网膜色素上皮(RPE)细胞增殖的影响及其机制。用0.5 - 11μmol/L的ATO培养RPE细胞24、48和72小时,通过MTT法检测其存活和生长情况。采用细胞免疫荧光和蛋白质印迹法检测RPE细胞中p27和增殖细胞核抗原(PCNA)的表达。实验组和对照组均呈现剂量依赖性。细胞处理3天时,在浓度为6μmol/L时获得50%抑制浓度。基于MTT结果,ATO的最佳浓度为6μmol/L。ATO处理第三天后,实验组细胞数量明显低于对照组。与对照组相比,细胞外基质(ECM)成分的表达降低。与对照组相比,在6μmol/L ATO处理72小时的细胞中,p27和PCNA的表达逐渐下降。实验组和对照组之间的差异具有显著性()。ATO能够通过调节ECM成分p27和PCNA的表达,以时间和剂量依赖的方式抑制RPE细胞的生长和增殖。因此,ATO可能为增殖性视网膜病变的治疗带来一种创新方法。

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