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首页> 外文期刊>Photodiagnosis and Photodynamic Therapy >Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro
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Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro

机译：肽转运蛋白PEPT1和ATP结合盒（ABC）转运蛋白ABCG2在体外基于5-氨基乙酰丙酸（ALA）的光细胞毒性中的关键作用

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摘要

Background: Recently, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is being widely used in cancer therapy owing to the tumor-specific accumulation of photosensitizing protoporphyrin IX (PplX) after the administration of ALA. In the present study, by focusing on genes involved in the porphyrin biosynthesis pathway, we aimed to explore biomarkers that are predictive for the efficacy of ALA-PDT. Methods: We used five lines of human gastric cancer cells to measure the ALA-based photocytotoxicity. ALA-induced production of PplX in cancer cells was quantified by fluorescence spectrophotometry. To examine the potential involvement of PEPT1 and ABCG2 in the ALA-PDT sensitivity, stable cell lines overexpressing PEPT1 were established and ABCG2-specific siRNA used.Results: We observed that three cell lines were photosensitive, whereas the other two cell lines were resistant to ALA-based photocytotoxicity. The ALA-based photocytotoxicity was found to be well correlated with intracellular PpiX levels, which suggests that certain enzymes and/or transporters involved in ALA-induced PplX production are critical determinants. We found that high expression of the peptide transporter PEPT1 (ALA influx transporter) and low expression of the ATP-binding cassette transporter ABCG2 (porphyrin efflux transporter) determined ALA-induced PplX production and cellular photosensitivity in vitro.
机译：背景：最近，由于ALA给药后，由于光敏性原卟啉IX（PplX）在肿瘤中的蓄积，基于5-氨基乙酰丙酸的光动力疗法（ALA-PDT）被广泛用于癌症治疗。在本研究中，通过关注与卟啉生物合成途径有关的基因，我们旨在探索可预测ALA-PDT疗效的生物标志物。方法：我们使用五种人胃癌细胞系来测量基于ALA的光细胞毒性。通过荧光分光光度法定量ALA诱导的癌细胞中PplX的产生。为了检测PEPT1和ABCG2在ALA-PDT敏感性中的潜在作用，建立了稳定表达PEPT1的稳定细胞系，并使用ABCG2特异性siRNA。结果：我们观察到3个细胞系具有光敏性，而其他2个细胞系具有抗性基于ALA的光细胞毒性。发现基于ALA的光细胞毒性与细胞内PpiX水平良好相关，这表明参与ALA诱导的PplX产生的某些酶和/或转运蛋白是关键的决定因素。我们发现，肽转运蛋白PEPT1（ALA流入转运蛋白）的高表达和ATP结合盒转运蛋白ABCG2（卟啉外排转运蛋白）的低表达决定了ALA诱导的PplX的产生和体外细胞光敏性。

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  • 来源
    《Photodiagnosis and Photodynamic Therapy》 |2012年第3期|p.204-214|共11页
  • 作者

    Yuichiro Hagiya; Yoshio Endo; Yutaka Yonemura; Kiwamu Takahashi; Masahiro Ishizuka; Fuminori Abe; Tohru Tanaka; Ichiro Okura; Motowo Nakajima; Toshihisa Ishikawa; Shun-ichiro Ogura;

  • 作者单位

    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan;

    Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan;

    NPO Organization to Support Peritoneal Dissemination Treatment, Japan;

    SBI ALApromo Co., Ltd., Izumi Garden Tower 19F, 1-6-1, Roppongi Minato-ku, Tokyo 106-6019, Japan;

    SBI ALApromo Co., Ltd., Izumi Garden Tower 19F, 1-6-1, Roppongi Minato-ku, Tokyo 106-6019, Japan;

    SBI ALApromo Co., Ltd., Izumi Garden Tower 19F, 1-6-1, Roppongi Minato-ku, Tokyo 106-6019, Japan;

    SBI ALApromo Co., Ltd., Izumi Garden Tower 19F, 1-6-1, Roppongi Minato-ku, Tokyo 106-6019, Japan;

    SBI ALApromo Co., Ltd., Izumi Garden Tower 19F, 1-6-1, Roppongi Minato-ku, Tokyo 106-6019, Japan;

    SBI ALApromo Co., Ltd., Izumi Garden Tower 19F, 1-6-1, Roppongi Minato-ku, Tokyo 106-6019, Japan;

    Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan;

    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan,Endowed Research Section (ALA), Frontier Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan;

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  • 正文语种 eng
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  • 关键词

    photodynamic therapy; ABCG2; PEPT1; 5-aminolevulinic acid; protoporphyrin IX;

    机译：光动力疗法;ABCG2;PEPT1;5-氨基乙酰丙酸;原卟啉IX;

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