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

J Photochem Photobiol B. 2015 Jul:148:82-87. doi: 10.1016/j.jphotobiol.2015.03.019. Epub 2015 Mar 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Liposomes
  • Mesoporphyrins
  • Photosensitizing Agents
  • RNA, Messenger
  • temoporfin