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Biological Consequences of PDT: tying up the loose ends

机译：PDT的生物学后果：束缚松散的末端

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While many of the determinants of photodynamic tumor eradication have been identified, the story is not yet complete. Fluorescent probes for reactive oxygen species (ROS) are seldom specific, and the role of different ROS in apoptosis vs. autophagy are not fully delineated. Moreover, the conflicting roles of autophagy as both a death and a survival pathway remain to be explained. Most tissue-culture studies are carried out in 20% oxygen although this is far in excess of the environment of malignant cells in vivo. And while apoptotic and/or autophagic death appears to account for the lethal effects of PDT, an effect on membrane recycling has now been identified. In this report, we summarize some recent experiments designed to examine the specificity of fluorescent ROS probes. We also demonstrate the ability of hydrogen peroxide to accelerate the autophagic response to PDT in an adhering cell line, the Iclc7 murine hepatoma. In this cell line, autophagy appears to be a pro-survival mechanism since a sub-line (KD) depleted in a critical autophagy protein (atg7) was more responsive to PDT than wild-type (WT) cells. There are clearly multiple determinants of direct tumor cell kill by PDT that depend on the PDT target, the ROS produced and phenotypic variations.
机译：尽管已经确定了许多根除光动力肿瘤的决定因素，但故事还不完整。活性氧（ROS）的荧光探针很少特异，并且不同ROS在凋亡与自噬中的作用尚未完全阐明。此外，自噬作为死亡和生存途径的冲突作用还有待解释。大多数组织培养研究都是在20％的氧气中进行的，尽管这远远超过了体内恶性细胞的环境。虽然凋亡和/或自噬死亡似乎是造成PDT致死的原因，但现在已经确定了对膜回收的影响。在这份报告中，我们总结了一些最近的实验，旨在检查荧光ROS探针的特异性。我们还证明了过氧化氢能够加速粘附细胞系Iclc7鼠肝癌中对PDT的自噬反应。在这种细胞系中，自噬似乎是一种生存机制，因为耗尽了关键自噬蛋白（atg7）的亚系（KD）比野生型（WT）细胞对PDT的反应更强。显然，PDT直接杀死肿瘤细胞有多个决定因素，这些决定因素取决于PDT靶标，产生的ROS和表型变异。

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