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首页> 外文期刊>Journal of cellular biochemistry. >Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in ovarian carcinoma cells.
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Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in ovarian carcinoma cells.

机译：干扰素调节因子-1介导干扰素-γ诱导的卵巢癌细胞凋亡。

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Interferon-gamma (IFN-gamma), as one of interferon family that regulates antiviral, antiproliferative, and immunomodulatory responses, has been implicated for the growth regulation of ovarian cancer cells. However, the molecular mechanisms are not yet fully defined. To analyze detailed mechanisms, the ovarian cancer cell lines (2774, PA-1, OVCAR-3, and SKOV-3) were treated with IFN-gamma. The growth of 2774 was most effectively suppressed than that of other cells in both time-course and dose-dependent experiments. The order of sensitivity in other cells was PA-1 OVCAR-3 > SKOV-3 (not responded at all). The DNA fragmentation and DAPI staining assays suggested that the IFN-gamma-mediated cytotoxicity could be triggered by apoptosis. The treatment induced IFN regulatory factor-1 (IRF-1) in two IFN-gamma-sensitive cells (2774, PA-1), whereas IRF-1 was not induced in two IFN-gamma-resistant cells (OVCAR-3, SKOV-3). The levels of p53 and p21WAF1 were not strikingly changed in all four cells. Interestingly, the expression of interleukin-converting enzyme (ICE, or caspase-1) was increased by the treatment in a kinetically consistent manner to the induction of IRF-1. However, CD95 (Fas/APO-1) was not changed. Apoptosis was greatly induced, when IRF-1 was transiently expressed in PA-1 without the treatment of IFN-gamma. However, it was repressed when IRF-1 together with IRF-2, an antagonist of IRF-1, were coexpressed. In addition, the effect of IFN-gamma was reduced in the 2774 and PA-1 cells stably expressing either IRF-1 antisense or IRF-2 sense, as shown by the cytotoxicity and FACS analysis. Furthermore, the IFN-gamma-induced apoptosis was greatly reduced, when inhibitors of ICE were treated into PA-1 cells. Taken together, these results suggest that IRF-1 directly mediates the IFN-gamma-induced apoptosis via the activation of caspase-1 gene expression in IFN-gamma-sensitive ovarian cancer cells.
机译：干扰素-γ（IFN-γ）作为调节抗病毒，抗增殖和免疫调节反应的干扰素家族之一，已被认为与卵巢癌细胞的生长调控有关。但是，分子机制尚未完全确定。为了分析详细的机制，用IFN-γ处理卵巢癌细胞系（2774，PA-1，OVCAR-3和SKOV-3）。在时间过程和剂量依赖性实验中，2774的生长均比其他细胞受到最有效的抑制。其他细胞中的敏感性顺序为PA-1 OVCAR-3> SKOV-3（完全不响应）。 DNA片段化和DAPI染色试验表明，凋亡可能触发IFN-γ介导的细胞毒性。该治疗在两个IFN-γ敏感细胞（2774，PA-1）中诱导了IFN调节因子-1（IRF-1），而在两个IFN-γ抵抗性细胞（OVCAR-3，SKOV）中未诱导IRF-1 -3）。在所有四个细胞中，p53和p21WAF1的水平均未发生显着变化。有趣的是，通过处理以与IRF-1的诱导在动力学上一致的方式增加了白介素转化酶（ICE或caspase-1）的表达。但是，CD95（Fas / APO-1）并未更改。如果在不使用IFN-γ的情况下在PA-1中短暂表达IRF-1，则会极大地诱导细胞凋亡。但是，当IRF-1与IRF-2（IRF-1的拮抗剂）共表达时，它被抑制。此外，如细胞毒性和FACS分析所示，在2774和稳定表达IRF-1反义或IRF-2有义的PA-1细胞中，IFN-γ的作用降低了。此外，当将ICE抑制剂处理到PA-1细胞中时，IFN-γ诱导的细胞凋亡大大降低。综上所述，这些结果表明，IRF-1通过激活IFN-γ敏感卵巢癌细胞中的caspase-1基因表达而直接介导IFN-γ诱导的凋亡。

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