Kalka K, Ahmad N, Criswell T, Boothman D, Mukhtar H
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Cancer Res. 2000 Nov 1;60(21):5984-7.
Photodynamic therapy (PDT) using the silicon phthalocyanine photo-sensitizer Pc 4 is an oxidative stress associated with the induction of apoptosis in many cancer cells in vitro and in vivo. The mechanisms of PDT-induced tumor cell killing leading to apoptosis are incompletely understood. Clusterin, a widely expressed glycoprotein, is induced in tissues regressing as a consequence of oxidative stress-mediated cell death. Treatment of apoptosis-sensitive human epidermoid carcinoma cells (A431) with PDT resulted in significant up-regulation of clusterin with a maximum at 12 h after treatment, whereas clusterin levels in Pc 4-PDT-treated, apoptosis-resistant, radiation-induced fibrosarcoma (RIF-1) cells remained unchanged. The i.v. administration of Pc 4 to mice bearing chemically or UVB radiation-induced skin papillomas, followed by light application, led to increased clusterin protein expression, peaking 24 h after the treatment, when tumor regression was apparently visible. These data, for the first time, demonstrate the involvement of clusterin in PDT-mediated cell death and during tumor regression. This may have relevance in improving the efficacy of PDT using pharmacological inducers of clusterin.
使用硅酞菁光敏剂Pc 4的光动力疗法（PDT）是一种与体外和体内多种癌细胞凋亡诱导相关的氧化应激。导致细胞凋亡的PDT诱导肿瘤细胞杀伤机制尚未完全明确。聚集素是一种广泛表达的糖蛋白，在因氧化应激介导的细胞死亡而消退的组织中被诱导产生。用PDT处理对凋亡敏感的人表皮样癌细胞（A431），导致聚集素显著上调，在处理后12小时达到最大值，而在经Pc 4 - PDT处理的、对凋亡有抗性的辐射诱导纤维肉瘤（RIF - 1）细胞中，聚集素水平保持不变。给携带化学诱导或UVB辐射诱导的皮肤乳头状瘤的小鼠静脉注射Pc 4，随后进行光照，导致聚集素蛋白表达增加，在处理后24小时达到峰值，此时肿瘤消退明显可见。这些数据首次证明了聚集素参与PDT介导的细胞死亡以及肿瘤消退过程。这可能与使用聚集素的药理学诱导剂提高PDT疗效有关。
