title: Breast cancer resistant protein (BCRP) is a molecular determinant of the outcome of photodynamic therapy (PDT) for centrally located early lung cancer.
abstract: The ATP-binding cassette (ABC) transporter protein, BCRP (breast cancer resistance protein)/ABCG2 pumps out some types of photosensitizers used in photodynamic therapy (PDT) and causes resistance to the antitumor effect of PDT. The purpose of this study was to investigate the association between the expression of BCRP and the efficacy of PDT using Photofrin, or the second-generation photosensitizer, NPe6, for centrally located early lung cancers. Using human epidermoid carcinoma cells, A431 cells and the BCRP-overexpressing A431/BCRP cells, we examined the effects of BCRP expression on the effect of PDT by cell viability assay in vitro, and investigated the expression of BCRP by immunohistochemical analysis in 81 tumor samples obtained from patients with centrally located early lung cancers. The A431/BCRP cells were more resistant to Photofrin-PDT than A431 cells in vitro, and Fumitremorgin C, a specific inhibitor of BCRP, reversed the resistance. However, there was no significant difference in the antitumor effect of NPe6-PDT between these cells. All of the 81 centrally located early lung cancer lesions were BCRP-positive (2+, 45 lesions; 1+, 30 lesions) and all the patients were male and heavy smokers (>30 pack-years). The expression of BCRP significantly affected the efficacy of Photofrin-PDT in cancer lesions > or =10mm in diameter (P=0.04). On the other hand, NPe6-PDT exhibited a strong antitumor effect, regardless of the expression status of BCRP. Photofrin may be a substrate of BCRP and be pumped out from the cells, therefore, BCRP may be a molecular determinant of the outcome of Photofrin-PDT.
authors.affiliation: Department of Thoracic Surgery, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. jusuda@tokyo-med.ac.jp
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Usuda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tsunoda
authors.forename: Shuji
authors.initials: S
authors.lastname: Ichinose
authors.forename: Taichirou
authors.initials: T
authors.lastname: Ishizumi
authors.forename: Keishi
authors.initials: K
authors.lastname: Ohtani
authors.forename: Sachio
authors.initials: S
authors.lastname: Maehara
authors.forename: Shoutarou
authors.initials: S
authors.lastname: Ono
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohira
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okunaka
authors.forename: Kinya
authors.initials: K
authors.lastname: Furukawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017323:Dihematoporphyrin Ether / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D017319:Photosensitizing Agents; D011166:Porphyrins; D017323:Dihematoporphyrin Ether; C053434:Talaporfin