Role of p53 and ATM in photodynamic therapy-induced apoptosis
Role of p53 and ATM in photodynamic therapy-induced apoptosis
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DOI：
10.1002/lsm.10213
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发表时间：
2003-01-01
影响因子：
2.4
通讯作者：
Fink, D
中科院分区：
文献类型：
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作者：
Heinzelmann-Schwarz, V;Fedier, A;Fink, D
背景和目的：光动力疗法 (PDT) 通过激光激活的光敏剂诱导细胞死亡，是对放疗和化疗耐药的肿瘤的一种治疗选择。 研究设计/材料和方法：我们研究了 m-THPC-PDT 是否通过坏死和/或凋亡诱导细胞死亡，以及这些反应是否受到 p53 和/或 ATM（两种癌症相关基因）的调节。通过 MTT 测定、台盼蓝排除以及 TUNEL 和 caspase3 裂解细胞凋亡测定来确定 atm(+/+)p53(+/+)、atm(+/+)p53(-/-) 和 atm(-/-)p53(-/-) 小鼠胚胎成纤维细胞对波长 652 nm 进行的 m-THPC-PDT 的敏感性。通过免疫印迹测定c-Abl蛋白水平。结果：m-THPC-PDT通过p53和共济失调毛细血管扩张突变(ATM)独立的非凋亡过程迅速诱导大部分细胞死亡。然而，在凋亡细胞亚群中，p53 的缺失会减少细胞凋亡，而 ATM 的额外缺失会进一步减少细胞凋亡。细胞凋亡与c-Abl水平成反比。结论：p53和ATM不是细胞坏死所必需的，但可能是PDT介导的细胞凋亡所必需的。 (C) 2003 Wiley-Liss, Inc.
Background and Objectives: Photodynamic therapy (PDT) induces cell death through a laser light-activated photosensitizer and is a treatment option for tumors resistant to radio- and chemo-therapy.Study Design/Materials and Methods: We investigated whether m-THPC-PDT induces cell death by necrosis and/or apoptosis, and whether these responses are modulated by p53 and/or ATM, two cancer-associated genes. Sensitivity of atm(+/+)p53(+/+), atm(+/+)p53(-/-), and atm(-/-)p53(-/-) mouse embryonic fibroblasts to m-THPC-PDT performed at a wavelength of 652 nm was determined by the MTT assay, trypan blue-exclusion, and the TUNEL and caspase3-cleavage apoptosis assays. c-Abl protein level was determined by immunoblotting.Results: m-THPC-PDT rapidly induced cell death in a substantial fraction of cells by p53- and Ataxia telangiectasia mutated (ATM)-independent non-apoptotic processes. However, in the subset of apoptotic cells, apoptosis was reduced by loss of p53 and was even more reduced by the additional loss of ATM. Apoptosis correlated inversely with c-Abl level.Conclusions: p53 and ATM are not required for necrosis, but may be required for PDT-mediated apoptosis. (C) 2003 Wiley-Liss, Inc.