Effects of photoactivated 5-aminolevulinic acid hexyl ester on MDR1 over-expressing human uterine sarcoma cells
Effects of photoactivated 5-aminolevulinic acid hexyl ester on MDR1 over-expressing human uterine sarcoma cells
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DOI：
10.1016/j.toxlet.2008.06.860
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发表时间：
2008-09-10
影响因子：
3.5
通讯作者：
Ho, Rodney J. Y.
中科院分区：
文献类型：
--
作者：
Chu, Ellie S. M.;Yow, Christine M. N.;Ho, Rodney J. Y.
用人子宫肉瘤细胞、MES-SA对照和表达MDR 1的MES-SA-Dx 5测定了MDR 1及其产物P-糖蛋白（P-gp）对5-氨基乙酰丙酸己酯（Hexyl-ALA）介导的光毒性的作用。MDR 1表达降低细胞内水平的己基-ALA代谢产物，原卟啉IX（PpIX）到有限的程度，可以逆转与P-gp抑制剂，维拉帕米。P-gp表达也降低了Hexyl-ALA的光敏性。更重要的是，光活化的Hexyl-ALA在mRNA和蛋白质水平上减少，而不改变管家GAPDH mRNA。这些发现表明，Hexyl-ALA可用于选择性降低P-gp表达，以克服对化疗药物如阿霉素和紫杉醇的耐药性。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
The role of multi-drug resistance (MDR1) and its product, P-glycoprotein (P-gp) on 5-aminolevulinic acid hexyl ester (Hexyl-ALA) mediated phototoxicity was determined with human uterine sarcoma cells, MES-SA control and MDR1 expressing MES-SA-Dx5. MDR1 expression reduced intracellular levels of the Hexyl-ALA metabolite, protoporphyrin IX (PpIX) to a limited degree and could be reversed with a P-gp inhibitor, verapamil. P-gp expression also reduced Hexyl-ALA photosensitivity. More importantly, photoactivated Hexyl-ALA reduced at the mRNA and protein levels without altering housekeeping GAPDH mRNA. These findings suggest that Hexyl-ALA could be used to selectively reduce P-gp expression in overcoming resistance to chemotherapy agents such as doxorubicin and paclitaxel. (C) 2008 Elsevier Ireland Ltd. All rights reserved.