Biologic activity of polyethylene glycol12000-interferon-alpha2b compared with interferon-alpha2b: gene modulatory and antigrowth effects in tumor cells.
Biologic activity of polyethylene glycol12000-interferon-alpha2b compared with interferon-alpha2b: gene modulatory and antigrowth effects in tumor cells.
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聚乙二醇12000-干扰素-α2b 与干扰素-α2b 的生物活性比较：肿瘤细胞中的基因调节和抗生长作用。
DOI：
10.1097/00002371-200305000-00004
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Leaman,DouglasW
中科院分区：
文献类型：
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作者：
Vyas,Keyur;Brassard,DianaL;DeLorenzo,MarcM;Sun,Yaping;Grace,MichaelJ;Borden,ErnestC;Leaman,DouglasW
在使用WM 9黑色素瘤或ACHN肾细胞癌细胞系的细胞培养研究中评估了干扰素-α2b（IFN-α2b）和聚乙二醇12000-IFN-α2b（PEG-IFN-α2b）的相对活性。当在使用每种IFN制剂的等效抗病毒单位进行的细胞增殖研究中检测时，干扰素-α2b和PEG-IFN-α2b具有相同的抗增殖活性。两种IFN制剂均不能有效诱导WM 9黑色素瘤细胞的凋亡，但通过膜联蛋白V染色评估，两者均轻微增加了经历凋亡的ACHN细胞的百分比。干扰素-α2b和PEG-IFN-α2b均激活信号转导子和转录激活子复合物，两种IFN制剂的复合物激活持续时间相似。通过北方印迹和定量实时逆转录-偶联聚合酶链反应（RT-PCR）在WM 9黑色素瘤、ACHN肾细胞癌、U937淋巴瘤、MOLT-4和Mono Mac 6白血病细胞系中评估不同IFN刺激基因的诱导。干扰素-α2b和PEG-IFN-α2b在这些肿瘤细胞系中具有等同的基因调节活性，尽管观察到细胞系特异性诱导模式。当与抗病毒50%抑制浓度（IC 50）值相比，剂量依赖性基因表达数据与细胞对IFN治疗的敏感性相关。总之，药物可比性和细胞敏感性数据表明剂量、时间、抗病毒活性和基因转录效应之间存在预测关系。因此，尽管IFN-α2b的比活性约为PEG-IFN-α2b的3倍，但当以相等的抗病毒单位应用于细胞时，两种制剂具有相同的体外生物活性。
The relative activities of interferon-α2b (IFN-α2b) and polyethylene glycol 12000–IFN-α2b (PEG–IFN-α2b) were assessed in cell culture studies using WM9 melanoma or ACHN renal cell carcinoma cell lines. Interferon-α2b and PEG–IFN-α2b had identical antiproliferative activities when tested in cell proliferation studies conducted with equivalent antiviral units of each IFN preparation. Neither IFN formulation was effective in inducing apoptosis in WM9 melanoma cells, but both increased slightly the percentage of ACHN cells undergoing apoptosis as assessed by Annexin V staining. Interferon-α2b and PEG–IFN-α2b both activated signal transducer and activator of transcription complexes, and the duration of complex activation was similar for both IFN formulations. Induction of different IFN-stimulated genes was assessed by Northern blotting and the quantitative real-time reverse transcription-coupled polymerase chain reaction (RT-PCR) in WM9 melanoma, ACHN renal cell carcinoma, U937 lymphoma, and MOLT-4 and Mono Mac 6 leukemia cell lines. Interferon-α2b and PEG–IFN-α2b had equivalent gene-modulatory activities within each of these tumor cell lines, although cell line–specific induction patterns were observed. When compared with the antiviral 50% inhibitory concentration (IC 50) values, the dose-dependent gene expression data correlated with cell sensitivity to IFN treatment. Together, the drug comparability and cell sensitivity data suggest a predictive relation between dose, time, antiviral activity, and gene transcription effects. Therefore, although the specific activity of IFN-α2b is approximately three times greater than PEG–IFN-α2b, the two preparations have identical in vitro biologic activities when applied to cells at equivalent antiviral units.