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Effect of hematoporphyrin monomethyl ether-mediated PDT on the mitochondria of canine breast cancer cells

机译:血卟啉单甲醚介导的PDT对犬乳腺癌细胞线粒体的影响

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摘要

Hematoporphyrin monomethyl ether (HMME) is a promising porphyrin-related photosensitize for photodynamic therapy (PDT). There still remains unknown changes regarding the mitochondrial in canine breast cancer cells treated with HMME-PDT. The aim of this study is to investigate the effect of HMME-PDT on structure and dysfunction of mitochondrial in cancer cells. The experimental approach included an initial study on the uptake of HMME using microscopic observation of the HMME-treated cells, optimization of the PDT-induced cell death by the MTT assay. These cells were then treated with HMME and a He-Ne laser at the wavelength of 632.8 nm following our optimized condition. Examination of mitochondrial changes by observing the stained cells under light microscope, mitochjondrial membrane potential flow cytometry, measuring the Ca~(2+), SOD/GSH activity, ATPase and MDA contents for the mitochondria functions. The kinetics of HMME uptake in CHMm cells was determined and its cytocolic instead of nuclear distribution was demonstrated. The dose of 16mM HMME-PDT combined with 2.8J/cm~2 laser irradiation was had the maximal impact on cell viability. This treatment resulted in structural changes in mitochondria that were accompanied with the loss of mitochjondrial membrane potential. As a result, HMME-PDT increased mitochondrial ROS, inhibited the enzymatic activities of mitochondrial SOD and GSH-Px, abolished mitochondrial ability in the uptake and release of calcium, and decreased mitochondrial ATPase activity. The combination of these abnormalities led to accumulation of ROS in mitochondrial to high levels, which in turn contributed to HMME-PDT-induced damages of mitochondrial structure and mitochondrial dysfunction.
机译:血卟啉单甲醚(HMME)是一种有前途的卟啉相关光敏剂,用于光动力疗法(PDT)。在用HMME-PDT处理的犬乳腺癌细胞中,关于线粒体的变化仍然未知。这项研究的目的是研究HMME-PDT对癌细胞线粒体结构和功能障碍的影响。实验方法包括使用HMME处理的细胞进行显微镜观察,通过MTT分析优化PDT诱导的细胞死亡来初步研究HMME的摄取。然后根据我们的优化条件,用HMME和He-Ne激光在632.8 nm的波长下处理这些细胞。通过在光学显微镜下观察染色的细胞,线粒体膜电位流式细胞仪,测量线粒体功能的Ca〜(2 +),SOD / GSH活性,ATPase和MDA含量来检查线粒体的变化。测定了CHMm细胞中HMME摄取的动力学,并证明了其细胞质而不是核分布。 16mM HMME-PDT联合2.8J / cm〜2激光辐照对细胞活力影响最大。这种治疗导致线粒体的结构变化,伴随着线粒体膜电位的丧失。结果,HMME-PDT增加了线粒体ROS,抑制了线粒体SOD和GSH-Px的酶活性,消除了线粒体吸收和释放钙的能力,并降低了线粒体ATPase的活性。这些异常的结合导致线粒体中ROS的积累达到高水平,进而导致HMME-PDT诱导的线粒体结构损伤和线粒体功能障碍。

著录项

  • 来源
    《Photodiagnosis and Photodynamic Therapy》 |2013年第4期|414-421|共8页
  • 作者单位

    Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University,Harbin, China,Department of Medicine, McMaster University, Hamilton, Canada;

    Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University,Harbin, China;

    Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University,Harbin, China;

    Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University,Harbin, China;

    Department of Medicine, McMaster University, Hamilton, Canada;

    Department of Veterinary, College of Animal Science and Veterinary Medicine, Qingdao AgriculturalUniversity, Qingdao, China,Department of Veterinary Clinic, College of Veterinary Medicine, South China Agricultural University,Guangzhou, China;

    Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University,Harbin, China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Hematoporphyrin monomethyl ether; CHMm cells; Mitochondrial dysfunction; Mitochondrial structure; PDT;

    机译:血卟啉单甲醚;CHMm细胞;线粒体功能障碍;线粒体结构;太平洋夏令时;

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