Photodynamic tumor therapy: Mitochondrial benzodiazepine receptors as a therapeutic target

Photodynamic tumor therapy: Mitochondrial benzodiazepine receptors as a therapeutic target
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DOI:
10.1007/bf03401728
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发表时间:
1998-01-01
期刊:
影响因子:
5.7
通讯作者:
Snyder, SH
Snyder, SH
中科院分区:
医学2区
文献类型:
--
作者:
Verma, A;Facchina, SL;Snyder, SH

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背景:光动力学疗法利用光敏剂如卟啉来治疗发光探针可触及的各种肿瘤。这种方法利用了癌细胞对卟啉的选择性保留。癌细胞也有线粒体benzodiazepine受体结合卟啉与高affinity.Methods:培养的癌细胞系暴露于卟啉和卟啉样化合物,然后用光照射。通过克隆形成试验测量该处理的细胞毒性。?线粒体benzodiazepine受体药理学研究使用[SH] PK11195结合到癌细胞匀浆和分离的肾脏mitochondrial membranes.Results:我们发现,卟啉类药物的治疗效力与线粒体benzodiazepine受体的亲和力密切相关。结论:卟啉光动力疗法是由线粒体苯二氮卓受体介导的。
Background: Photodynamic therapy employs photosensitive agents such as porphyrins to treat a variety of tumors accessible to light-emitting probes. This approach capitalizes on the selective retention of porphyrins by cancer cells. Cancer cells also have elevated levels of mitochondrial benzodiazepine receptors which bind porphyrins with high affinity.Methods: Cultured cancer cell lines were exposed to porphyrin and porphyrin-like compounds and then irradiated with light. Cytotoxicity of this treatment was measured via clonogenic assays. ?Mitochondrial benzodiazepine receptor pharmacology was studied using [SH] PK11195 binding to cancer cell homogenates and isolated kidney mitochondrial membranes.Results: We show that therapeutic potencies of porphyrins correlate closely with affinities for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors.Conclusion: We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.