Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug-resistant human gastric cancer cell lines

被引:12
作者
Chen, Jingjing [1 ]
Mao, Lina [2 ,3 ]
Liu, Shuping [4 ]
Liang, Yanling [4 ]
Wang, Sicheng [5 ]
Wang, Yeyu [1 ]
Zhao, Qiang [6 ]
Zhang, Xiaojing [7 ]
Che, Yanjun [8 ]
Gao, Lijing [9 ]
Liu, Tianjun [2 ,3 ]
机构
[1] Changzhi Med Coll, Heping Hosp, Cent Lab, Changzhi City 046000, Shanxi Province, Peoples R China
[2] Peking Union Med Coll, Inst Biomed Engn, Mol Design & Nanotechnol Lab, Tianjin 300192, Peoples R China
[3] Chinese Acad Med Sci, Tianjin 300192, Peoples R China
[4] Changzhi Med Coll, Heping Hosp, Dept Dermatol, Changzhi City 046000, Shanxi Province, Peoples R China
[5] Changzhi Med Coll, Heping Hosp, Urinary Surg, Changzhi City 046000, Shanxi Province, Peoples R China
[6] Changzhi Med Coll, Heping Hosp, Oncol Surg, Changzhi City 046000, Shanxi Province, Peoples R China
[7] Changzhi Med Coll, Dept Pharmacol, Changzhi City 046000, Shanxi Province, Peoples R China
[8] Changzhi Med Coll, Heping Hosp, Dept Osteol, Changzhi City 046000, Shanxi Province, Peoples R China
[9] Changzhi Med Coll, Dept Physiol, Changzhi City 046000, Shanxi Province, Peoples R China
关键词
Photodynamic therapy; DTP; Multidrug resistance; Cytotoxicity; MEDIATED PHOTODYNAMIC THERAPY; IN-VITRO; LOCALIZATION; TRANSPORTER; EFFICACY; MCF-7;
D O I
10.1016/j.jphotobiol.2015.08.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Photodynamic therapy (PDT) has been considered to be a possible candidate approach in combating multidrug resistance (MDR) phenomenon during the treatment of cancer. To investigate the photocytotoxicity of a novel porphyrin-based photosensitizer, meso-5[rho-DTPA-aminophenyl]-10, 15, 20-triphenyl-porhyrin (DTP) (Fig. 1A), on MDR cells, the intracellular DTP uptake, phototoxicity and subcellular DTP localization were studied by using a human gastric cancer MGC803 cell line and its paclitaxel selected subline MGC803/PA expressing MDR phenotype. No significant difference was observed in intracellular DTP accumulation between sensitive and resistant cell lines after exposure to 1.56 mu M concentration for 6 h. DTP-PDT induced significant photocytotoxicity on both MGC803 and MGC803/PA cell lines and the photokilling was greater in MGC803 cell line in comparison to MGC803/PA. The fluence that caused 50% cell death was 4.42 and 6.29 J/cm(2) in MGC803 and MGC803/PA cell lines, respectively. The presence of Pgp inhibitors verapamil and cyclosporin A could not modify the intracellular DTP level in MGC803/PA cell line and the phototoxic effects. DTP was localized at lysosomes of MGC803 cell line but at lysosomes and mitochondria of MGC803/PA. Our results indicated that DTP-mediated PDT could eradicate gastric cancer cells whether or not they express MDR although the efficacy is slightly reduced in the MDR cells. The photokilling in MDR cells could not be altered by MDR inhibitor verapamil. The slightly different photocytotoxicity between sensitive and resistant cell lines could not explained by classical Pgp MDR and might be attributed to the differential intracellular DTP localization sites. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:186 / 193
页数:8
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