细胞毒性核糖核酸酶的抗肿瘤功效,ranpirnase A549人肺癌裸鼠异种移植。

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李我,Kalota Gewirtz, Shogen K

细胞毒性核糖核酸酶的抗肿瘤功效,ranpirnase A549人肺癌裸鼠异种移植。

外科杂志2007;1 - 2月27 (1):299 - 307。

PubMed ID
17352247 (在PubMed
]
文摘

背景:细胞毒性核糖核酸酶,ranpirnase (ONC ONCONASE),可能有前途的治疗理念作为替代顺铂治疗肺癌,由于抑制蛋白质合成的t-RNA乳沟。材料与方法:A549和NCI-H1975人类非小细胞肺癌细胞株培养的存在和缺乏ONC。使用一个单独测定细胞毒性监测。利用倒置的阶段和荧光显微镜,我们研究引起的细胞凋亡是否在gefitinib-induced ONC apoptosis-resistant A549肿瘤细胞。治疗有效性ONC研究通过单个和多个政府对A549人类非小细胞肺癌(NSCLC),包括肿瘤由顺铂以前无法治疗。ONC-induced ATP水平变化也监测到了non-localized磷谱先生。结果:ONC显著抑制A549细胞生长的肿瘤。引起的细胞凋亡明显ONC剂量依赖性的方式。在动物实验中,多个小剂量ONC比一个大单剂量更有效的抑制肿瘤的生长和减少副作用,可能由于漏水的肿瘤血管正常化。ONC结合顺铂A549肿瘤显著降低肿瘤的生长。 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.

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