title: Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells.
abstract: BACKGROUND
  Since the ATP-binding cassette transporter ABCG2 plays a physiologically significant role of porphyrin efflux from living cells, the expression of ABCG2 may influences the efficacy of photodynamic therapy (PDT). In this study, we evaluated the effect of gefitinib, a potent ABCG2 inhibitor, on 5-aminolevulinic acid (5-ALA)-PDT in brain tumor cell lines in vitro.
  
  
  METHODS
  Four human glioma cell lines (U87MG, U118MG, A172, and T98G) and a malignant meningioma cell line (IOMM-Lee) were incubated with gefitinib (0.01-1.0μM) before incubation with 5-ALA (1mM). The effects gefitinib on intracellular protoporphyrin IX (PpIX), mRNA and protein expression of ABCG2, and PDT were evaluated, in vitro.
  
  
  RESULTS
  At concentrations of 0.1μM or higher, gefitinib enhanced intracellular levels of PpIX in a dose-dependent manner in all those cell lines. Gefitinib decreased mRNA and plasma membrane protein expression of ABCG2, and efficiently enhanced the effect of 5-ALA-PDT in malignant brain tumor cells.
  
  
  CONCLUSIONS
  Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.
authors: Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan; Department of Neurosurgery, Pu Nan Hospital, Shanghai, People's Republic of China.
authors: Wei
authors: W
authors: Sun
authors: Yoshinaga
authors: Y
authors: Kajimoto
authors: Hiroto
authors: H
authors: Inoue
authors: Shin-Ichi
authors: S
authors: Miyatake
authors: Toshihisa
authors: T
authors: Ishikawa
authors: Toshihiko
authors: T
authors: Kuroiwa
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077156:Gefitinib; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011799:Quinazolines; D000622:Aminolevulinic Acid; D000077156:Gefitinib