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  • Title: Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells.
    Author: Sun W, Kajimoto Y, Inoue H, Miyatake S, Ishikawa T, Kuroiwa T.
    Journal: Photodiagnosis Photodyn Ther; 2013 Feb; 10(1):42-50. PubMed ID: 23465372.
    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. MATERIALS AND 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. CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.
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