新型潜在光动力疗法策略使用 5-氨基酮戊酸治疗卵巢透明细胞癌。

Novel potential photodynamic therapy strategy using 5-Aminolevulinic acid for ovarian clear-cell carcinoma.

机构信息

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya, 466-8550, Japan.

Department of Gynecology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan; Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

出版信息

Photodiagnosis Photodyn Ther. 2018 Mar;21:121-127. doi: 10.1016/j.pdpdt.2017.11.013. Epub 2017 Nov 28.

DOI:10.1016/j.pdpdt.2017.11.013

PMID:29196245

Abstract

BACKGROUND

Photodynamic therapy (PDT) is known as a minimally invasive treatment for cancer. 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizing agent protoporphyrin IX (PpIX). Patients with ovarian clear-cell carcinoma (CCC) have poorer prognoses than those of patients with other histological CCC types. We evaluated the efficacy of ALA-PDT on CCC cells in vitro.

METHODS

We used seven human CCC cell lines to measure the cytotoxicity of ALA-PDT. PpIX production in cancer cells was measured using a micro-plate reader. Quantitative real-time PCR was performed to assess the mRNA levels of genes involved in the accumulation of PpIX in cancer cells. Additionally, we measured the enhancement in cytotoxicity with the use of an ABCG2 inhibitor.

RESULTS

We found that three cell lines were highly sensitive to ALA-PDT. In contrast, one cell line was resistant to ALA-PDT. The cytotoxicity of ALA-PDT varied among CCC cell lines. The IC50 values of ALA-PDT for the CCC cell lines had a wide range (30-882μM). The cytotoxicity of ALA-PDT was correlated with the intracellular PpIX accumulation. The cell lines sensitive to ALA-PDT expressed PEPT1 (an ALA uptake transporter). The cell line resistant to ALA-PDT expressed ABCG2 (a PpIX export transporter). In the resistant cell line, a combination treatment with both ALA and an ABCG2 inhibitor resulted in the promotion of cytotoxic sensitivity.

CONCLUSION

The present study revealed the efficacy of ALA-PDT against CCC with chemoresistance in vitro.

摘要

背景

光动力疗法（PDT）被认为是一种治疗癌症的微创方法。5-氨基酮戊酸（ALA）是光敏剂原卟啉 IX（PpIX）的前体。与其他组织学类型的卵巢透明细胞癌（CCC）患者相比，卵巢透明细胞癌（CCC）患者的预后更差。我们评估了 ALA-PDT 对体外 CCC 细胞的疗效。

方法

我们使用七种人 CCC 细胞系来测量 ALA-PDT 的细胞毒性。使用微孔板读取器测量癌细胞中 PpIX 的产生。通过定量实时 PCR 评估参与癌细胞中 PpIX 积累的基因的 mRNA 水平。此外，我们还测量了使用 ABCG2 抑制剂增强细胞毒性的效果。

结果

我们发现三种细胞系对 ALA-PDT 高度敏感。相比之下，有一种细胞系对 ALA-PDT 有抗性。ALA-PDT 的细胞毒性在 CCC 细胞系之间存在差异。ALA-PDT 的 CCC 细胞系的 IC50 值范围很广（30-882μM）。ALA-PDT 的细胞毒性与细胞内 PpIX 积累相关。对 ALA-PDT 敏感的细胞系表达 PEPT1（ALA 摄取转运体）。对 ALA-PDT 有抗性的细胞系表达 ABCG2（PpIX 外排转运体）。在耐药细胞系中，ALA 和 ABCG2 抑制剂的联合治疗促进了细胞毒性敏感性。