Experimental therapy using interferon-gamma and anti-Fas antibody against oral malignant melanoma cells
Experimental therapy using interferon-gamma and anti-Fas antibody against oral malignant melanoma cells
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DOI：
10.1097/00008390-200510000-00007
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发表时间：
2005-10-01
影响因子：
2.2
通讯作者：
Tagawa, T
中科院分区：
文献类型：
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作者：
Kamei, T;Inui, M;Tagawa, T
Fas/FasL信号系统在多种不同细胞类型的化疗诱导的凋亡中起重要作用。在干扰素- γ (IFN-gamma)治疗后，我们之前报道过口腔恶性黑色素瘤细胞系（MMN9， PMP， MAA， HMG）体外Fas表达显著增加，并且使用ifn - γ和抗Fas抗体（CH-11）联合治疗在MMN9细胞中显示出协同抗增殖作用。已经有一些使用CH-11的体外研究，但很少有关于其体内抗肿瘤作用的报道。在本研究中，我们在小鼠模型中研究了针对MMN9的抗fas抗体的实验治疗，并对BALB/c裸鼠肿瘤组织进行了组织学检查。第一次给药20天后，同时接受ifn - γ和CH-11治疗的动物抗肿瘤效果增加53.8% （P = 0.0018）。在组织学研究中，联合给药组在末端脱氧核苷酸转移酶介导的缺口末端标记染色中呈阳性，免疫染色中Fas表达水平较载药组显著升高。这些结果表明，使用ifn - γ和抗fas抗体通过调节fas介导的细胞凋亡来抗癌治疗的有效性。此外，用一种通用的caspase抑制剂（benzyloxycarbonyl- vala - ala - asp - fluorom甲基酮）抑制ifn - γ / ch -11诱导的细胞凋亡，可显著减少体外细胞死亡。在这些条件下，Bcl-2没有发生切割，这表明在MMN9细胞中caspase激活与Bcl-2切割之间存在关系。
The Fas/FasL signalling system plays an important role in chemotherapy-induced apoptosis in several different cell types. After interferon-gamma (IFN-gamma) treatment, we have previously reported a significant increase in Fas expression in oral malignant melanoma cell lines (MMN9, PMP, MAA, HMG) in vitro, and combination therapy using IFN-gamma and anti-Fas antibody (CH-11) has shown a synergistic anti-proliferative effect in MMN9 cells. There have been several in-vitro studies using CH-11, but there are few reports of its anti-tumour effect in vivo. In this study, we investigated experimental therapy using anti-Fas antibody against MMN9 in vivo in a mouse model, and histologically examined tumour tissue removed from BALB/c nude mice. Animals that received both IFN-gamma and CH-11 showed a 53.8% increase in anti-tumour effect (P = 0.0018) 20 days after the first administration. In the histological study, the combined administration group tested positive in terminal deoxynucleotidyl transferase-mediated nick end labelling staining, and showed significantly increased levels of Fas expression on immunostaining compared with the vehicle group. These results show the efficacy of anticancer therapy using IFN-gamma and anti-Fas antibody via the modulation of Fas-mediated apoptosis. Moreover, inhibition of IFN-gamma/CH-11-induced apoptosis with a general caspase inhibitor (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) reduced cell death significantly in vitro. Bcl-2 cleavage did not occur under these conditions, suggesting a relationship between caspase activation and Bcl-2 cleavage in MMN9 cells.