Wang Y, Herman T S, Teicher B A
Dana-Farber Cancer Institute, Boston, MA.
Br J Cancer. 1989 May;59(5):722-6. doi: 10.1038/bjc.1989.152.
Several new complexes of platinum with positively charged cellular dyes have been synthesised in an effort to find chemotherapeutic drugs with increased antitumour cytotoxicity. As part of this effort, the direct cytotoxicities of some of these complexes as well as their ability to inhibit bleomycin potentially lethal damage repair (PLDR) was studied in vitro in a squamous cancer cell line of human origin (SCC-25). All of the new agents were more cytotoxic against exponentially growing than against plateau phase cell cultures. Exposure of cells to non-lethal drug concentrations for between 1 and 6 h led to measurable inhibition of bleomycin PLDR in the case of each drug tested. In order of decreasing ability to inhibit bleomycin PLDR, Pt(fast black)2, Pt(thioflavin)2 and Pt(thionin)2 were more effective than CDDP, while Pt(methylene blue)2, Pt(Rh-123)2 and Pt(pyronin Y)2 were less effective. The most directly cytotoxic agents were Pt(thioflavin)2, Pt(pyronin Y)2 and Pt(Rh-123)2 which also proved to be the least selectively toxic drugs towards exponential versus plateau phase cells. These results indicate that several of the new platinum complexes may be effective cytotoxic agents as well as effective inhibitors of DNA repair process following exposure of cells to other DNA interactive modalities.
为了找到具有更高抗肿瘤细胞毒性的化疗药物，人们合成了几种铂与带正电荷细胞染料的新型配合物。作为这项工作的一部分，在人源鳞状癌细胞系（SCC - 25）中对其中一些配合物的直接细胞毒性及其抑制博来霉素潜在致死性损伤修复（PLDR）的能力进行了体外研究。所有新试剂对指数生长期细胞的细胞毒性均高于对平台期细胞培养物的毒性。将细胞暴露于非致死性药物浓度1至6小时后，每种测试药物均导致可测量的博来霉素PLDR抑制。按照抑制博来霉素PLDR能力的降序排列，Pt（固绿）2、Pt（硫黄素）2和Pt（硫堇）2比顺铂更有效，而Pt（亚甲蓝）2、Pt（罗丹明123）2和Pt（派洛宁Y）2则效果较差。细胞毒性最强的试剂是Pt（硫黄素）2、Pt（派洛宁Y）2和Pt（罗丹明123）2，它们对指数期细胞与平台期细胞的选择性毒性也最低。这些结果表明，几种新型铂配合物可能是有效的细胞毒性药物，也是细胞在暴露于其他DNA相互作用方式后DNA修复过程的有效抑制剂。
