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: Jingjing Chen, Lina Mao, Shuping Liu, Yanling Liang, Sicheng Wang, Yeyu Wang, Qiang Zhao, Xiaojing Zhang, Yanjun Che, Lijing Gao, Tianjun Liu
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 151 Pg. 186-93 (Oct 2015) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 26302181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Photosensitizing Agents
• Porphyrins
• meso-5-(p-DTPA-aminophenyl)-10, 15, 20-triphenyl-porhyrin
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Cell Line, Tumor
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Paclitaxel (pharmacology)
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry, pharmacokinetics, pharmacology)
• Porphyrins (chemistry, pharmacology)
• Stomach Neoplasms (drug therapy, metabolism, pathology)