Predictors of therapeutic efficacy of 5-aminolevulinic acid-based photodynamic therapy in human prostate cancer
| Autor: | Taku Nakayama, Takashi Karashima, Chiaki Kawada, Shun-ichiro Ogura, Keiji Inoue, Hideo Fukuhara, Hitomi Seki, Shinkuro Yamamoto |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Abcg2 medicine.medical_treatment Biophysics Protoporphyrins Photodynamic therapy Dermatology Prostate cancer chemistry.chemical_compound DU145 Cell Line Tumor LNCaP medicine Humans Pharmacology (medical) Photosensitizing Agents biology Protoporphyrin IX business.industry Cancer Prostatic Neoplasms Aminolevulinic Acid medicine.disease Oncology chemistry Photochemotherapy Cancer cell biology.protein Cancer research business |
| Zdroj: | Photodiagnosis and photodynamic therapy. 35 |
| ISSN: | 1873-1597 |
| Popis: | Background 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. Materials and methods 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 Results 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. Conclusion The ABCG2 transporter is a useful predictor of the therapeutic effect of ALA-PDT on human prostate cancer cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect