Regulatory pathways in photodynamic therapy induced apoptosis
Regulatory pathways in photodynamic therapy induced apoptosis
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DOI：
10.1039/b315237e
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Hendrickx, N
中科院分区：
文献类型：
--
作者：
Agostinis, P;Buytaert, E;Hendrickx, N
光动力疗法是一种基于光吸收化合物(光敏剂)和光照射的被批准的治疗几种类型的肿瘤和某些良性疾病的方法。在分子氧存在的情况下，积聚在癌症组织中的光敏剂的光激活导致局部产生活性氧物种，从而杀死肿瘤细胞。线粒体是光动力疗法诱导靶细胞凋亡机制的中心协调者。最近的研究表明，伴随着线粒体外膜的通透性(导致胞浆中几种促凋亡因子的释放和效应半胱氨酸酶的激活)，调节信号通路以光敏剂、PDT剂量和细胞依赖的方式被激活。由丝裂原活化蛋白激酶成员及其下游靶点如环氧合酶-2调控的信号通路似乎对癌细胞对光动力疗法的敏感性起着关键的调节作用。了解导致PDT诱导细胞凋亡的分子事件，以及癌细胞如何逃脱凋亡死亡，应该能够为药物设计和治疗提供更合理的方法。
Photodynamic therapy is an approved treatment for several types of tumors and certain benign diseases, based on the use of a light-absorbing compound ( photosensitizer) and light irradiation. In the presence of molecular oxygen, light-activation of the photosensitizer, which accumulates in cancer tissues, leads to the local production of reactive oxygen species that kill the tumor cells. Mitochondria are central coordinators of the mechanisms by which PDT induces apoptosis in the target cells. Recent studies indicate that concomitant to the permeabilization of the outer mitochondrial membrane (which leads to the release of several apoptogenic factors in the cytosol and to the activation of effector caspases), regulatory signaling pathways are activated in a photosensitizer, PDT dose and cell-dependent fashion. Signaling pathways regulated by members of mitogen activated protein kinases and their downstream targets, such as cyclooxygenase-2, appear to critically modulate cancer cell sensitivity to PDT. Understanding the molecular events that contribute to PDT-induced apoptosis, and how cancer cells can evade apoptotic death, should enable a more rationale approach to drug design and therapy.