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首页> 外文期刊>Photodiagnosis and Photodynamic Therapy >Bis (3,5-diiodo-2,4,6-trihydroxyphenyl) squaraine photodynamic therapy induces in vivo tumor ablation by triggering cytochrome c dependent mitochondria mediated apoptosis
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Bis (3,5-diiodo-2,4,6-trihydroxyphenyl) squaraine photodynamic therapy induces in vivo tumor ablation by triggering cytochrome c dependent mitochondria mediated apoptosis

机译：Bis（3,5-diiodo-2,4,6-trihydroxyphenyl）squaraine光动力疗法通过触发细胞色素c依赖的线粒体介导的凋亡诱导体内肿瘤消融

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Background: Despite findings that photodynamic treatment with bis (3,5-diiodo-2,4,6-trihydroxyphenyl) squaraine initiated tumor regression in mice skin, queries regarding its mode of action - answers to which will be functional to design clinical trials on squaraine based photodynamic therapy - remain unanswered. Our investigation reveals the in vivo mechanism of action of the photosensitizer. Methods: Skin tumor was induced in Swiss albino mice using 7,12-dimethyl benzanthacene. After the intraperitoneal administration of the dye in tumor induced mice, its concentration in subcellular fractions of the tumor tissue was determined fluorimetrically. Cytochrome c release from the mitochondrial membrane after the photodynamic treatment was analyzed. The observations stemming from this part lead to histopathological examination of tumor tissues. Apoptotic markers like caspase-3, Bcl-2 and Bax were also studied. Results: Major portion of the dye accumulated in the mitochondria. Cytochrome c leakage from mitochondria after squaraine PDT suggests loss of mitochondrial membrane integrity, which was further confirmed by the results of histopathological analysis. The activity of caspase-3 was elevated, expression of Bcl-2 diminished and that of Bax increased - all these results show enhancement of apoptosis in the tumor region after the treatment. Conclusions: The results lead to the elucidation of mechanism of tumor destruction which proves to be mitochondria mediated apoptotic damage of tumor tissue. The study assumes significance since it defines the in vivo mode of action of a photosensitizer. Also, the query of how a squaraine based photosensitizer evokes tumor response is being dealt with here, for the first time.
机译：背景：尽管发现双（3,5-二碘-2-2,4,6-三羟苯基）方酸的光动力治疗可引起小鼠皮肤肿瘤消退，但有关其作用方式的疑问-答案将对设计临床试验起作用基于方酸的光动力疗法-尚未得到解答。我们的研究揭示了光敏剂的体内作用机理。方法：使用7,12-二甲基苯并蒽在瑞士的白化病小鼠中诱发皮肤肿瘤。在肿瘤诱导的小鼠中腹膜内施用该染料后，用荧光法测定其在肿瘤组织的亚细胞级分中的浓度。分析了光动力处理后从线粒体膜释放的细胞色素c。来自此部分的观察结果导致了肿瘤组织的组织病理学检查。还研究了凋亡标记物，如caspase-3，Bcl-2和Bax。结果：大部分染料积累在线粒体中。方酸PDT后线粒体细胞色素c的泄漏表明线粒体膜完整性的丧失，这由组织病理学分析结果进一步证实。 caspase-3的活性升高，Bcl-2的表达减少，而Bax的表达增加-所有这些结果表明治疗后肿瘤区域的细胞凋亡增强。结论：该结果阐明了肿瘤破坏的机制，该机制被证明是线粒体介导的肿瘤细胞凋亡损伤。该研究具有重要意义，因为它定义了光敏剂的体内作用方式。同样，关于基于方酸的光敏剂如何引起肿瘤反应的询问在此首次得到处理。

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