RRC ID 44492
著者 Yamamoto M, Fujita H, Katase N, Inoue K, Nagatsuka H, Utsumi K, Sasaki J, Ohuchi H.
タイトル Improvement of the efficacy of 5-aminolevulinic acid-mediated photodynamic treatment in human oral squamous cell carcinoma HSC-4.
ジャーナル Acta Med Okayama
Abstract Ever since protoporphyrin IX (PpIX) was discovered to accumulate preferentially in cancer cells after 5-aminolevulinic acid (ALA) treatment, photodynamic treatment or therapy (PDT) has been developed as an exciting new treatment option for cancer patients. However, the level of PpIX accumulation in oral cancer is fairly low and insufficient for PDT. Ferrochelatase (FECH) and ATP-binding cassette transporter G2 (ABCG2) are known to regulate PpIX accumulation. In addition, serum enhances PpIX export by ABCG2. We investigated here whether and how inhibitors of FECH and ABCG2 and their combination could improve PpIX accumulation and PDT efficacy in an oral cancer cell line in serum-containing medium. ABCG2 inhibitor and the combination of ABCG2 and FECH inhibitors increased PpIX in the presence of fetal bovine serum (FBS) in an oral cancer cell line. Analysis of ABCG2 gene silencing also revealed the involvement of ABCG2 in the regulation of PpIX accumulation. Inhibitors of FECH and ABCG2, and their combination increased the efficiency of ALA-PDT even in the presence of FBS. ALA-PDT-induced cell death was accompanied by apoptotic events and lipid peroxidation. These results suggest that accumulation of PpIX is determined by the activities of ABCG2 and FECH and that treatment with a combination of their inhibitors improves the efficacy of PDT for oral cancer, especially in the presence of serum.
巻・号 67(3)
ページ 153-64
公開日 2013-1-1
DOI 10.18926/AMO/50408
PMID 23804138
MeSH ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters / genetics Amino Acid Chloromethyl Ketones / pharmacology Aminolevulinic Acid / pharmacology* Apoptosis / drug effects Blood Proteins / pharmacology Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Caspase Inhibitors / pharmacology Cell Line, Tumor Deferoxamine / pharmacology Ferrochelatase / antagonists & inhibitors Gene Silencing Humans Lipid Peroxidation / drug effects Mouth Neoplasms / drug therapy* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Neoplasm Proteins / genetics Photochemotherapy / methods* Photosensitizing Agents / pharmacology Protoporphyrins / metabolism Siderophores / pharmacology
IF 0.642
引用数 13
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
ヒト・動物細胞