title: Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug-resistant human gastric cancer cell lines.
abstract: 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-[ρ-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 μM concentration for 6h. 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.
authors: Central Laboratory of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Jingjing
authors: J
authors: Chen
authors: Molecular Design and Nanotechnology Laboratory of Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin City 300192, People's Republic of China.
authors: Lina
authors: L
authors: Mao
authors: Department of Dermatology of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Shuping
authors: S
authors: Liu
authors: Department of Dermatology of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Yanling
authors: Y
authors: Liang
authors: Urinary Surgery of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Sicheng
authors: S
authors: Wang
authors: Central Laboratory of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Yeyu
authors: Y
authors: Wang
authors: Oncological Surgery of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Qiang
authors: Q
authors: Zhao
authors: Department of Pharmacology of Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Xiaojing
authors: X
authors: Zhang
authors: Department of Osteology of Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Yanjun
authors: Y
authors: Che
authors: Department of Physiology of Changzhi Medical College, Changzhi City, Shanxi Province 046000, People's Republic of China.
authors: Lijing
authors: L
authors: Gao
authors: Molecular Design and Nanotechnology Laboratory of Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin City 300192, People's Republic of China. Electronic address: liutianjuntj@126.com.
authors: Tianjun
authors: T
authors: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017319:Photosensitizing Agents; D011166:Porphyrins; C000614535:meso-5-(p-DTPA-aminophenyl)-10, 15, 20-triphenyl-porhyrin; D017239:Paclitaxel
keywords: Cytotoxicity; DTP; Multidrug resistance; Photodynamic therapy