Petru E, Berger M R, Zeller W J, Kaufmann M
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg, F.R.G.
Eur J Cancer Clin Oncol. 1988 Jun;24(6):1027-32. doi: 10.1016/0277-5379(88)90153-8.
In vitro activity of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-ala-17-E2) at three concentrations in transplanted MXT mammary carcinoma in B6D2F1 mice and autochthonous methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats, as well as in 30 human primary breast carcinomas using the bilayer soft agar assay is described. Eighty-five per cent of MXT tumors showed a more than 70% inhibition of colony formation following CNC-ala-17-E2. In the MNU-induced model this high degree of inhibition was not observed: only 5% of individual tumors showed an inhibition up to 70%, but a superiority of the hormone-linked agent over the unlinked single agents was nevertheless discernible. In contrast, in human breast carcinomas a response at this sensitivity level could not be assessed. Thus, in the MXT mammary carcinoma the in vitro results paralleled previous findings in vivo, whereas in the MNU-induced autochthonous tumor model this close in vivo-in vitro correlation was not observed. The discrepancy between in vivo and in vitro results found in the autochthonous rat model indicates that hormone-linked nitrosoureas should not necessarily be abandoned for the treatment of human breast carcinoma on the basis of negative in vitro results alone.
描述了1-(2-氯乙基)-1-亚硝基氨基甲酰基-L-丙氨酸-雌二醇-17-酯（CNC-ala-17-E2）在三种浓度下对B6D2F1小鼠移植的MXT乳腺癌、Sprague-Dawley大鼠原位甲基亚硝基脲（MNU）诱导的乳腺癌以及30例人原发性乳腺癌的体外活性，采用双层软琼脂试验进行检测。85%的MXT肿瘤在CNC-ala-17-E2处理后集落形成受到超过70%的抑制。在MNU诱导的模型中未观察到如此高程度的抑制：只有5%的单个肿瘤显示抑制率高达70%，但与未连接的单一药物相比，激素连接药物的优势仍然明显。相比之下，在人乳腺癌中无法评估这种敏感性水平的反应。因此，在MXT乳腺癌中，体外结果与先前的体内研究结果一致，而在MNU诱导的原位肿瘤模型中未观察到这种体内-体外的密切相关性。在原位大鼠模型中发现的体内和体外结果之间的差异表明，不应仅基于体外阴性结果就必然放弃激素连接的亚硝基脲用于治疗人乳腺癌。
