文献类型：期刊文献

英文题名：Development of a multifunctional luciferase reporters system for assessing endoplasmic reticulum-targeting photosensitive compounds

作者：Lin, Shengchao[1,2];Zhang, Lingling[1,2];Lei, Kecheng[1,2];Zhang, Anle[1,2];Liu, Ping[3];Liu, Jianwen[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Dept Mol & Cellular Pharmacol, Biomed Nanotechnol Ctr, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 200032, Peoples R China

年份：2014

卷号：19

期号：6

起止页码：927

外文期刊名：CELL STRESS & CHAPERONES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000344873100018)】；

基金：This work was supported by Shanghai Committee of Science and Technology (No. 13140902300), Nano Science and Technology Special Funding of Shanghai Committee of Science and Technology (No. 11 nm0503700), the Shanghai Committee of Science and Technology [grant 11DZ2260600] and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Photodynamic therapy (PDT); Endoplasmic reticulum targeting; GRP78 promoter activity; CHOP promoter activity; Antitumor property

摘要：Photodynamic therapy (PDT) is a recently developed antitumor modality utilizing the generation of reactive oxygen species (ROS), through light irradiation of photosensitizers (PSs) localized in tumor. Interference with proper functioning of endoplasmic reticulum (ER) by ER-targeting PDT is a newly proposed strategy to achieve tumor cell death. The aim of this study is to establish a multifunctional model to screen and assess ER-targeting PSs based on luciferase reporters system. Upregulation of GRP78 is a biomarker for the onset of ER stress. CHOP is a key initiating player in ER stress-induced cell death. Here, the most sensitive fragments of GRP78 and CHOP promoters responding to ER-targeting PDT were mapped and cloned into pGL3-basic vector, forming -702/GRP78-Luc and -443/CHOP-Luc construct, respectively. We demonstrated that -702/GRP78-Luc expression can be used to indicate the ER-targeting of PSs, meanwhile estimate the ROS level induced by low-dose ER-targeting PDT. Moreover, the luciferase signaling of -443/CHOP-Luc showed highly consistence with apoptosis rate caused by ER-targeting PDT, suggesting that -443/CHOP-Luc can evaluate the antitumor properties of PSs. Hypericin, Foscan (R) and methylene blue were applied to verify the sensitivity and reliability of our model. These results proved that GRP78-CHOP model may be suitable to screen ER-targeting photosensitive compounds with lower cost and higher sensitivity than traditional ways.