Drees M, Dengler W M, Hendriks H R, Kelland L R, Fiebig H H
Department of Internal Medicine, University of Freiburg, FRG.
Eur J Cancer. 1995;31A(3):356-61. doi: 10.1016/0959-8049(94)00513-5.
Cycloplatam is a novel platinum compound which has shown anti-tumour activity in murine tumour models. In this study, cycloplatam was found to have anti-tumour activity in vitro and in vivo in human tumour models. In 15 cell lines (mainly ovarian), cycloplatam showed similar cytotoxicity as cisplatin, using the sulphorhodamine B assay. Determination of the resistance factor (IC50 of cisplatin-resistant divided by IC50 of parental cell line) clearly showed lower values for cycloplatam than for cisplatin. In the parental ovarian cell line CH1 and the cisplatin-resistant CH1 cisR model, we observed no cross-resistance of cycloplatam and cisplatin. The in vitro anti-tumour activity was confirmed in human tumour xenografts using the clonogenic assay. Mean IC70 values of cycloplatam were 0.54 microgram/ml (1.25 microM) and of cisplatin 0.42 microgram/ml (1.4 microM), respectively. In the murine subcutaneously implanted ADJ/PC6 plasmacytoma in vivo cycloplatam showed less activity than cisplatin, with a 2-fold smaller therapeutic index than cisplatin. In ovarian cancer xenografts cycloplatam was less active than cisplatin. However, anti-tumour activity of cycloplatam in lung cancer xenografts was quite different from cisplatin. In LXFS 538, a model moderately sensitive to cisplatin, a partial remission was observed, but in LXFL 529, a cisplatin-sensitive model, cycloplatam was inactive, cycloplatam thus demonstrating a different spectrum of anti-tumour activity. Based on these results, further preclinical investigations with other tumours, such as cisplatin-sensitive and -resistant gastric cancer models, are warranted with cycloplatam.
环铂是一种新型铂化合物，已在小鼠肿瘤模型中显示出抗肿瘤活性。在本研究中，发现环铂在人肿瘤模型中具有体内外抗肿瘤活性。使用磺酰罗丹明B测定法，在15种细胞系（主要是卵巢细胞系）中，环铂显示出与顺铂相似的细胞毒性。耐药因子（顺铂耐药细胞系的IC50除以亲本细胞系的IC50）的测定清楚地表明，环铂的值低于顺铂。在亲本卵巢细胞系CH1和顺铂耐药的CH1 cisR模型中，我们未观察到环铂和顺铂之间的交叉耐药性。使用克隆形成测定法在人肿瘤异种移植模型中证实了其体外抗肿瘤活性。环铂的平均IC70值分别为0.54微克/毫升（1.25微摩尔），顺铂的平均IC70值为0.42微克/毫升（1.4微摩尔）。在小鼠皮下植入的ADJ/PC6浆细胞瘤体内，环铂的活性低于顺铂，治疗指数比顺铂小2倍。在卵巢癌异种移植模型中，环铂的活性低于顺铂。然而，环铂在肺癌异种移植模型中的抗肿瘤活性与顺铂有很大不同。在对顺铂中度敏感的LXFS 538模型中，观察到部分缓解，但在对顺铂敏感的LXFL 529模型中，环铂无活性，因此环铂显示出不同的抗肿瘤活性谱。基于这些结果，有必要使用环铂对其他肿瘤进行进一步的临床前研究，如对顺铂敏感和耐药的胃癌模型。
