Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan.
Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan; Center for Photodynamic Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan.
Photodiagnosis Photodyn Ther. 2021 Sep;35:102452. doi: 10.1016/j.pdpdt.2021.102452. Epub 2021 Jul 21.
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 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.
The ABCG2 transporter is a useful predictor of the therapeutic effect of ALA-PDT on human prostate cancer cells.
光动力疗法（PDT）是一种微创癌症治疗方法。然而，其治疗前列腺癌的疗效尚不完全清楚。本研究旨在探讨 5-氨基酮戊酸（ALA）-PDT 治疗前列腺癌细胞的疗效预测因子。
采用人前列腺癌细胞系 PC-3、22Rv1、DU145 和 LNCap 研究 ALA-PDT 对原卟啉 IX（PpIX）细胞内积累的影响，通过流式细胞术进行检测。通过 MTT（3-(4,5-二甲基噻唑基-2)-2,5-二苯基四氮唑溴盐）测定评估 ALA-PDT 的细胞毒性。通过定量实时聚合酶链反应（qRT-PCR）全面评估卟啉代谢相关酶和转运蛋白的 mRNA 水平。通过 Western blot 评估蛋白表达。使用 PC-3 和 22Rv1 建立异种移植模型，然后进行病理分析以确定 ALA-PDT 的治疗效果。
PC-3 和 LNCap 细胞 PpIX 积累高，对 ALA-PDT 敏感，而 22Rv1 和 DU145 细胞 PpIX 积累低，对 ALA-PDT 不敏感。ALA-PDT 诱导的细胞毒性与 PpIX 积累呈负相关。体外研究鉴定出三磷酸腺苷结合盒转运体亚家族 G2（ABCG2）转运体二聚体为治疗反应的预测因子。体内 ABCG2 转运体免疫组织化学染色显示 PC-3 细胞低表达，22Rv1 细胞高表达，ALA-PDT 诱导的肿瘤组织退变在 PC-3 细胞中大于 22Rv1 细胞。
ABCG2 转运体是 ALA-PDT 治疗人前列腺癌细胞疗效的有用预测因子。
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