Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol -: A superoxide dismutase inhibitor
Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol -: A superoxide dismutase inhibitor
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DOI：
10.1074/jbc.m209125200
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发表时间：
2003-01-03
影响因子：
4.8
通讯作者：
Jakóbisiak, M
中科院分区：
文献类型：
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作者：
Golab, J;Nowis, D;Jakóbisiak, M
光动力学疗法（PDT）是一种由光敏剂和可见光组成的两阶段治疗，是一种很有前途的实体瘤治疗方式。越来越多的证据表明，暴露于亚致死剂量PDT的区域中的肿瘤细胞可以通过导致细胞死亡不足的拯救反应来响应。我们决定研究超氧化物歧化酶（SOD）在PDT有效性中的作用，并研究SOD抑制剂2-甲氧乙烯醚（2-McOE（2））是否能够增强这种治疗方案的抗肿瘤作用。在初步实验中，我们观察到PDT诱导癌细胞中MnSOD的表达，而不是Cu，Zn-SOD。预处理的癌细胞与细胞可渗透的SOD模拟物，锰（II）-四（4-苯甲酸）卟啉氯化物，和瞬时转染MnSOD基因导致PDT的有效性降低。用2-MeOE 2预孵育抑制肿瘤细胞中SOD活性，与PDT联合应用，在3种小鼠和5种人肿瘤细胞系中产生协同抗肿瘤作用。联合治疗在体内也有效，可延缓肿瘤生长并延长荷瘤小鼠的存活期。我们的结论是MnSOD活性的抑制2-MeOE 2是一种有效的治疗方式能够增强PDT的抗肿瘤效果。
Photodynamic therapy (PDT), a promising therapeutic modality for the management of solid tumors, is a two-phase treatment consisting of a photosensitizer and visible light. Increasing evidence indicates that tumor cells in regions exposed to sublethal doses of PDT can respond by rescue responses that lead to insufficient cell death. We decided to examine the role of superoxide dismutases (SODs) in the effectiveness of PDT and to investigate whether 2-methoxyestradiol (2-McOE(2)), an inhibitor of SODs, is capable of potentiating the antitumor effects of this treatment regimen. In the initial experiment we observed that PDT induced the expression of MnSOD but not Cu,Zn-SOD in cancer cells. Pretreatment of cancer cells with a cell-permeable SOD mimetic, Mn(II)-tetrakis(4-benzoic acid)porphyrin chloride, and transient transfection with the MnSOD gene resulted in a decreased effectiveness of PDT. Inhibition of SOD activity in tumor cells by preincubation with 2-MeOE2 produced synergistic antitumor effects when combined with PDT in 3 murine and 5 human tumor cell lines. The combination treatment was also effective in vivo producing retardation of the tumor growth and prolongation of the survival of tumor-bearing mice. We conclude that inhibition of MnSOD activity by 2-MeOE2 is an effective treatment modality capable of potentiating the antitumor effectiveness of PDT.