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十六烷氧基丙基9-[2-(膦酰甲氧基)乙基]鸟嘌呤（HDP-PMEG）对眼部异常增殖的抗增殖特性

Antiproliferative property of hexadecyloxypropyl 9-[2-(phosphonomethoxy) ethyl] guanine (HDP-PMEG) for unwanted ocular proliferation.

作者信息

Hou Jiangping, Li Yuli, Zhou Zhonglou, Valiaeva Nadejda, Beadle James R, Hostetler Karl, Freeman William R, Hu Dan-Ning, Chen Hao, Cheng Lingyun

机构信息

Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang,China.

出版信息

Mol Vis. 2011 Mar 2;17:627-37.

PMID:21386925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3049735/
Abstract

PURPOSE

To investigate the safety and inhibitory effects of hexadecyloxypropyl 9-[2-(phosphonomethoxy) ethyl] guanine (HDP-PMEG) on ocular cell proliferation and collagen matrix contraction.

METHODS

For the antiproliferation studies, various ocular cell monolayers were exposed to HDP-PMEG, PMEG, 5-fluorouracil (5-FU), and daunorubicin (DNB). For the collagen contraction studies, retinal pigment epithelium (RPE) cells seeded onto type I collagen lattices were exposed for a single 5- or 50-min period to various concentrations of HDP-PMEG or 5-FU. For the cytotoxicity study, trypan blue exclusion tests were performed using a human Müller cell line. Cytotoxicity was determined up to 4 days after treatment.

RESULTS

The proliferation of RPE cells, scleral fibroblasts, vessel endothelial cells, and ocular melanoma cells can all be significantly inhibited by HDP-PMEG. Its inhibitory effects on those cells were uniformly stronger than that of 5-FU. Contraction of the collagen matrix containing RPE cells was significantly inhibited by HDP-PMEG and by 5-FU at concentrations of 20 µM and 2,000 µM, respectively, as compared with controls (p<0.05). The safety profile of HDP-PMEG was significantly better than 5-FU and daunorubicin. The ocular therapeutic index is 1,100 for HDP-PMEG, 17.2 for 5-FU, and 1.25 for daunorubicin.

CONCLUSIONS

HDP-PMEG possesses a significant inhibitory effect on the proliferation of RPE, retinal glial cells, scleral fibroblasts, and ocular melanoma cells. HDP-PMEG is also genotoxic and may be used as a single short application for the modulation of unwanted ocular proliferation.

摘要

目的

研究十六烷氧基丙基9-[2-(膦酰甲氧基)乙基]鸟嘌呤（HDP-PMEG）对眼细胞增殖和胶原基质收缩的安全性及抑制作用。

方法

在抗增殖研究中，将各种眼细胞单层暴露于HDP-PMEG、PMEG、5-氟尿嘧啶（5-FU）和柔红霉素（DNB）。在胶原收缩研究中，将接种于I型胶原晶格上的视网膜色素上皮（RPE）细胞暴露于不同浓度的HDP-PMEG或5-FU中5分钟或50分钟。在细胞毒性研究中，使用人 Müller 细胞系进行台盼蓝排斥试验。在处理后长达4天测定细胞毒性。

结果

HDP-PMEG可显著抑制RPE细胞、巩膜成纤维细胞、血管内皮细胞和眼黑色素瘤细胞的增殖。其对这些细胞的抑制作用均强于5-FU。与对照组相比，分别在20 μM和2000 μM浓度下，HDP-PMEG和5-FU可显著抑制含RPE细胞的胶原基质收缩（p<0.05）。HDP-PMEG的安全性显著优于5-FU和柔红霉素。HDP-PMEG的眼治疗指数为1100，5-FU为17.2，柔红霉素为1.25。

结论

HDP-PMEG对RPE、视网膜神经胶质细胞、巩膜成纤维细胞和眼黑色素瘤细胞的增殖具有显著抑制作用。HDP-PMEG也具有遗传毒性，可作为单次短期应用来调节不必要的眼部增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/3948a528a286/mv-v17-627-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/21c2825899a3/mv-v17-627-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/752829d3b7b1/mv-v17-627-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/1fb9e9ce3cae/mv-v17-627-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/e205aceff3cf/mv-v17-627-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/3948a528a286/mv-v17-627-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/21c2825899a3/mv-v17-627-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/752829d3b7b1/mv-v17-627-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/1fb9e9ce3cae/mv-v17-627-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/e205aceff3cf/mv-v17-627-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbeb/3049735/3948a528a286/mv-v17-627-f5.jpg

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