Predictors of therapeutic efficacy of 5-aminolevulinic acid-based photodynamic therapy in human prostate cancer

• Published in: Photodiagnosis and photodynamic therapy Vol. 35; p. 102452
• Main Authors: Yamamoto, Shinkuro, Fukuhara, Hideo, Seki, Hitomi, Kawada, Chiaki, Nakayama, Taku, Karashima, Takashi, Ogura, Shun-ichiro, Inoue, Keiji
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2021
• Subjects: 5-aminolevulinic acid; ABCG2 transporter; Human prostate cancer; Photodynamic therapy; ABCG2 transporter; Photodynamic therapy; 5-aminolevulinic acid; Human prostate cancer
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2021.102452

•Intracellular protoporphyrin IX accumulation and cytotoxicity of ALA-PDT differ among prostate cancer cell lines.•Analysis of the expression level of ABCG2 transporter dimer is useful as a predictor of the sensitivity of ALA-PDT in vitro.•Immunohistochemical analysis for the ABCG2 transporter may be useful as a predictor of the sensitivity of ALA-PDT in vivo. Photodynamic therapy (PDT) is a minimally invasive cancer therapy. However, its therapeutic efficacy for prostate cancer is not yet fully understood. In this study, the predictors of therapeutic efficacy of 5-aminolevulinic acid-based PDT (ALA-PDT) on prostate cancer cells are investigated. The human prostate cancer cell lines, PC-3, 22Rv1, DU145, and LNCap were used to investigate the effects of ALA-PDT on protoporphyrin IX (PpIX) intracellular accumulation, which was measured by flow cytometry. The cytotoxicity of ALA-PDT was evaluated by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The levels of porphyrin metabolism-related enzyme and transporter mRNA were comprehensively evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated by Western blot. A xenograft model was created using PC-3 and 22Rv1, and then, pathological analysis was performed to determine the therapeutic effect of ALA-PDT PC-3 and LNCap cells showed high accumulation of PpIX and high sensitivity to ALA-PDT, while 22Rv1 and DU145 showed low accumulation of PpIX and low sensitivity to ALA-PDT. ALA-PDT-induced cytotoxicity correlated negatively with PpIX accumulation. The in vitro assays identified the ATP-binding cassette transporter subfamily G2 (ABCG2) transporter dimer as a predictor of treatment response. In vivo immunohistochemical staining of ABCG2 transporter showed low expression in PC-3 cells and high expression in 22Rv1 cells, and ALA-PDT-induced tumor tissue degeneration was greater in PC-3 cells than in 22Rv1 cells. The ABCG2 transporter is a useful predictor of the therapeutic effect of ALA-PDT on human prostate cancer cells.