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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Antitumor efficacy of the cytotoxic RNase, ranpirnase, on A549 human lung cancer xenografts of nude mice.
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Antitumor efficacy of the cytotoxic RNase, ranpirnase, on A549 human lung cancer xenografts of nude mice.

机译：细胞毒性核糖核酸酶ranpirnase对A549人肺癌裸鼠异种移植物的抗肿瘤功效。

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BACKGROUND: The cytotoxic RNase, ranpirnase (ONCONASE, ONC), may have promising therapeutic implication as an alternative for cisplatin for the treatment of lung cancer, due to inhibition of protein synthesis by t-RNA cleavage. MATERIALS AND METHODS: A549 and NCI-H1975 human NSCLC cell lines were cultured in the presence and absence of ONC. Cytotoxicity was monitored using a clonogenic assay. Using an inverted phase and fluorescence microscope, we studied whether apoptosis was induced by ONC in gefitinib-induced apoptosis-resistant A549 tumor cells. The therapeutic effectiveness of ONC was studied via single and multiple administrations on A549 human non-small cell lung cancer (NSCLC), including tumors previously untreatable by cisplatin. ONC-induced changes in ATP levels were also monitored by non-localized phosphorus MR spectroscopy. RESULTS: ONC significantly inhibited the cell growth of A549 tumors. Apoptosis was significantly induced by ONC in a dose-dependent manner. In animal studies, multiple small doses of ONC were more effective than one large single dose for the inhibition of tumor growth with reduced side-effects, probably due to the normalization of leaky tumor vessels. ONC in combination with cisplatin significantly reduced tumor growth of A549 tumors. In large tumors, including those unsuccessfully treated with cisplatin, ONC showed inhibition of tumor growth, while a second treatment of cisplatin did not. During monitoring by non-localized phosphorus MR spectroscopy, ATP levels decreased, likely due to ONC-induced inhibition of oxygen consumption (QO2). CONCLUSION: ONC significantly inhibited tumor growth of A549 NSCLC cells in both in vitro and in vivo studies. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients.
机译：背景：由于t-RNA裂解可抑制蛋白质合成，因此作为顺铂的替代品，具有细胞毒性的RNase，ranpirnase（ONCONASE，ONC）可能具有广阔的治疗意义。材料与方法：在存在和不存在ONC的情况下培养A549和NCI-H1975人NSCLC细胞系。使用克隆形成测定法监测细胞毒性。使用反相和荧光显微镜，我们研究了ONC是否在吉非替尼诱导的凋亡抗性A549肿瘤细胞中诱导了细胞凋亡。通过对A549人非小细胞肺癌（NSCLC）进行单次或多次给药研究了ONC的治疗效果，其中包括先前无法用顺铂治疗的肿瘤。还通过非局部磷MR光谱监测ONC诱导的ATP水平变化。结果：ONC明显抑制A549肿瘤细胞的生长。 ONC以剂量依赖性方式明显诱导细胞凋亡。在动物研究中，多次小剂量的ONC在抑制肿瘤生长方面具有比一次大的单剂量更有效的副作用，这可能是由于渗漏的肿瘤血管正常所致。 ONC与顺铂联合可显着降低A549肿瘤的肿瘤生长。在大肿瘤中，包括未用顺铂治疗的肿瘤，ONC显示出对肿瘤生长的抑制作用，而第二次顺铂治疗则没有。在通过非局部磷MR光谱监测期间，ATP水平下降，可能是由于ONC诱导的氧气消耗抑制（QO2）。结论：在体外和体内研究中，ONC均能显着抑制A549 NSCLC细胞的肿瘤生长。这项研究表明ONC在治疗NSCLC癌症患者中具有重要的潜在临床用途。

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