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.