Effect of FosPeg® mediated photoactivation on P-gp/ABCB1 protein expression in human nasopharyngeal carcinoma cells

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2015-07, Vol.148, p.82-87
• Main Authors: Wu, R W K, Chu, E S M, Huang, Z, Xu, C S, Ip, C W, Yow, C M N
• Format: Article
• Language: English
• Subjects: ATP Binding Cassette Transporter, Subfamily B - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; Carcinoma; Cell Line, Tumor; Drug Resistance, Neoplasm - drug effects; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; Humans; Light; Liposomes - chemistry; Liposomes - pharmacology; Liposomes - therapeutic use; Mesoporphyrins - chemistry; Mesoporphyrins - pharmacology; Mesoporphyrins - therapeutic use; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - drug therapy; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Photochemotherapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; RNA, Messenger - metabolism
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2015.03.019

Multidrug resistance (MDR) refers to the ability of cancer cells to develop cross resistance to a range of anticancer drugs which are structurally and functionally unrelated. P-glycoprotein (P-gp) is the best studied MDR phenotype in photodynamic therapy (PDT) treated cells. Our pervious study demonstrated that FosPeg® mediated PDT is effective to NPC cell line models. In this in vitro study, the expression of MDR1 gene and its product P-gp in undifferentiated, poorly differentiated and well differentiated human nasopharyngeal carcinoma (NPC) cells were investigated. The influence of P-gp efflux activities on photosensitizer FosPeg® was also examined. Regardless of the differentiation status, PDT tested NPC cell lines all expressed P-gp protein. Results indicated that FosPeg® photoactivation could heighten the expression of MDR1 gene and P-gp transporter protein in a dose dependent manner. Up to 2-fold increase of P-gp protein expression were seen in NPC cells after FosPeg® mediated PDT. Interestingly, our finding demonstrated that FosPeg® mediated PDT efficiency is independent to the MDR1 gene and P-gp protein expression in NPC cells. FosPeg® itself is not the substrate of P-gp transporter protein and no efflux of FosPeg® were observed in NPC cells. Therefore, the PDT efficiency would not be affected even though FosPeg® mediated PDT could induce MDR1 gene and P-gp protein expression in NPC cells. FosPeg® mediated PDT could be a potential therapeutic approach for MDR cancer patients.