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以若丹明123在CD8细胞中的蓄积作为替代指标,研究盐酸千金藤素在体内对P-糖蛋白的调节作用。

Using rhodamine 123 accumulation in CD8 cells as a surrogate indicator to study the P-glycoprotein modulating effect of cepharanthine hydrochloride in vivo.

作者信息

Li Han, Yan Zhang, Ning Wang, Xiao-Juan Guo, Cai-Hong Zang, Jin-Hua Jiang, Fang Ma, Qing-Duan Wang

机构信息

School of Pharmaceutical Sciences, Zhengzhou University, Zhenzhou 45001, Henan, China.

出版信息

J Biomed Biotechnol. 2011;2011:281651. doi: 10.1155/2011/281651. Epub 2011 Jun 30.

DOI:10.1155/2011/281651
PMID:21765632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3134191/
Abstract

The purpose of this study was the use of rhodamine 123 (Rho123) accumulation in peripheral blood CD8(+)cells as a surrogate indicator to evaluate the modulating effect of P-glycoprotein (P-gp) inhibitors in the multidrug resistance (MDR) tumor-bearing mouse model. Rho123 was administered to mice, and the fluorescence level in CD8(+) cells was measured. Cepharanthine hydrochloride (CH) and verapamil (VER), two P-gp inhibitors, were administered to mice 1 hour prior to Rho123 administration in vivo or added to peripheral blood 1 hour prior to Rho123 addition ex vivo. The tumor inhibition effect of 5-fluorouracil/adriamycin/cisplatin (FAP) protocol plus CH was also investigated. A concentration- or dose-response relationship was shown between the concentration and dose of CH and Rho123 accumulation or the antitumor activity. In conclusion, the measurement of Rho123 accumulation in CD8(+) cells provides a surrogate assay for the screening of candidate P-gp inhibitors in preclinical trials, and CH is effective in modulating P-gp-mediated MDR in vivo.

摘要

本研究的目的是利用外周血CD8(+)细胞中罗丹明123(Rho123)的蓄积作为替代指标,评估P-糖蛋白(P-gp)抑制剂在多药耐药(MDR)荷瘤小鼠模型中的调节作用。给小鼠注射Rho123,并测量CD8(+)细胞中的荧光水平。在体内给小鼠注射Rho123前1小时给予两种P-gp抑制剂盐酸千金藤素(CH)和维拉帕米(VER),或在体外添加Rho123前1小时将其添加到外周血中。还研究了5-氟尿嘧啶/阿霉素/顺铂(FAP)方案加CH的抑瘤效果。CH的浓度或剂量与Rho123蓄积或抗肿瘤活性之间呈现浓度-或剂量-反应关系。总之,测量CD8(+)细胞中Rho123的蓄积为临床前试验中筛选候选P-gp抑制剂提供了一种替代检测方法,并且CH在体内有效调节P-gp介导的MDR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/d1d09913c67b/JBB2011-281651.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/84f119257895/JBB2011-281651.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/cba042986586/JBB2011-281651.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/630d1f20b177/JBB2011-281651.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/d1d09913c67b/JBB2011-281651.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/84f119257895/JBB2011-281651.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/cba042986586/JBB2011-281651.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/630d1f20b177/JBB2011-281651.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e6/3134191/d1d09913c67b/JBB2011-281651.004.jpg

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