Kessel David
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
Photochem Photobiol. 2008 May-Jun;84(3):809-14. doi: 10.1111/j.1751-1097.2007.00267.x. Epub 2007 Dec 20.
Photodynamic therapy (PDT) directed against the endoplasmic reticulum (ER) is also known to target antiapoptotic Bcl-2 family proteins. This effect is associated with the initiation of both apoptosis, a cell death pathway, and autophagy, an organelle recycling system that can lead to survival or cell death. In this study, we examined the ability of the Bcl-2 antagonist HA14-1 to promote the photodynamic efficacy of PDT directed at the ER. At concentrations that independently caused only a small loss of viability, HA14-1 markedly enhanced the proapoptotic and phototoxic effects of ER photodamage. These results provide additional evidence that the antiapoptotic properties of Bcl-2 constitute an important determinant of photokilling, and demonstrate that synergistic effects can result when PDT is coupled with pharmacologic suppression of Bcl-2 function.
针对内质网（ER）的光动力疗法（PDT）也已知会靶向抗凋亡的Bcl-2家族蛋白。这种效应与细胞凋亡（一种细胞死亡途径）和自噬（一种细胞器回收系统，可导致存活或细胞死亡）的启动有关。在本研究中，我们检测了Bcl-2拮抗剂HA14-1促进针对内质网的光动力疗法的光动力疗效的能力。在仅独立导致少量活力丧失的浓度下，HA14-1显著增强了内质网光损伤的促凋亡和光毒性作用。这些结果提供了额外的证据，证明Bcl-2的抗凋亡特性是光杀伤的重要决定因素，并表明当光动力疗法与Bcl-2功能的药理学抑制相结合时可产生协同效应。
