Breast cancer resistant protein (BCRP) is a molecular determinant of the outcome of photodynamic therapy (PDT) for centrally located early lung cancer

Jitsuo Usuda, Yoshihiko Tsunoda, Shuji Ichinose, Taichirou Ishizumi, Keishi Ohtani, Sachio Maehara, Shoutarou Ono, Hidemitsu Tsutsui, Tatsuo Ohira, Tetsuya Okunaka, Kinya Furukawa, Yoshikazu Sugimoto, Harubumi Kato, Norihiko Ikeda

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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 ≥10 mm 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.

Original languageEnglish
Pages (from-to)198-204
Number of pages7
JournalLung Cancer
Volume67
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

Keywords

  • Breast cancer resistant protein (BCRP)
  • Centrally located early lung cancer
  • Lung cancer
  • Photodynamic therapy (PDT)

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Fingerprint Dive into the research topics of 'Breast cancer resistant protein (BCRP) is a molecular determinant of the outcome of photodynamic therapy (PDT) for centrally located early lung cancer'. Together they form a unique fingerprint.

Cite this