eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

被引:12
作者
Fan, Zhichao [1 ,2 ,7 ]
Cui, Xiaojun [2 ,3 ]
Wei, Dan [1 ]
Liu, Wei [6 ]
Li, Buhong [4 ]
He, Hao [1 ]
Ye, Huamao [5 ]
Zhu, Naishuo [2 ,3 ]
Wei, Xunbin [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Shanghai 200030, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China
[3] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Lab Mol Immunol, Shanghai 200433, Peoples R China
[4] Fujian Normal Univ, Fujian Prov Key Lab Photon Technol, Key Lab Optoelect Sci & Technol Med, Minist Educ, Fuzhou, Fujian, Peoples R China
[5] Second Mil Univ, Changhai Hosp, Dept Urol, Shanghai, Peoples R China
[6] Sanford Burnham Prebys Med Discovery Inst, Cell Death & Survival Networks Program, La Jolla, CA USA
[7] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA USA
关键词
ELONGATION-FACTOR; 1A; CD4(+) T-CELL; EXPRESSION LEVELS; DENDRITIC CELL; PHAGE DISPLAY; IN-VITRO; APOPTOSIS; PROTEINS; ACCUMULATION; COMBINATION;
D O I
10.1038/srep25353
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 x 10(6) M-1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.
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页数:9
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