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螺锗——一种新型抗肿瘤药物,在体外对一系列“标准”抗肿瘤药物表现出无交叉耐药性。

Spirogermanium--a novel antitumour agent expressing a lack of cross-resistance in vitro with a range of 'standard' antitumour drugs.

作者信息

Hill B T, Whelan R D

出版信息

Invest New Drugs. 1986;4(4):359-65. doi: 10.1007/BF00173508.

Abstract

We have used a series of drug resistant continuous tumour cell lines of murine, hamster or human origin, to screen in vitro for new drugs effective at overcoming resistance expressed to clinically useful antitumour drugs. We have established that spirogermanium appears to express a unique lack of cross resistance to a wide range of 'standard' antitumour drugs including 5-fluorouracil, cisplatin, methotrexate, vincristine and adriamycin, as judged by its equivalent effectiveness in reducing survival, measured by clonogenic assays, of the parental and drug-resistant sublines following 24 hour in vitro treatments. Spirogermanium was also able to overcome the multidrug resistance exhibited by the colchicine-resistant mutant CHRC5 cells and a subline of vincristine-resistant MCF-7 human breast carcinoma cells, following 1 or 24 hour drug treatments. These preclinical studies suggest that this novel compound may prove a potentially useful agent for inclusion in 'non-cross-resistant drug combinations'.

摘要

我们使用了一系列源自小鼠、仓鼠或人类的耐药性连续肿瘤细胞系,在体外筛选能够有效克服对临床常用抗肿瘤药物所表现出的耐药性的新药。我们已经确定,通过克隆形成试验测定,在体外进行24小时处理后,螺锗对包括5-氟尿嘧啶、顺铂、甲氨蝶呤、长春新碱和阿霉素在内的多种“标准”抗肿瘤药物似乎表现出独特的无交叉耐药性,这是根据其在降低亲本和耐药亚系存活率方面的等效有效性来判断的。在进行1或24小时的药物处理后,螺锗还能够克服秋水仙碱耐药突变体CHRC5细胞和长春新碱耐药的MCF-7人乳腺癌细胞亚系所表现出的多药耐药性。这些临床前研究表明,这种新型化合物可能被证明是一种潜在有用的药物,可纳入“非交叉耐药药物组合”中。

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