Han I, Nguyen T, Yang L Y, Khokhar A R, Perez-Soler R
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Anticancer Drugs. 1994 Feb;5(1):64-8. doi: 10.1097/00001813-199402000-00010.
Liposomal cis-bis-neodecanato-trans-R,R-1,2-diaminocyclohexaneplatinum (11) (L-NDDP) is a liposome-entrapped platinum complex that has shown partial lack of cross-resistance with cisplatin in human colon carcinoma LoVo cells. We studied the drug accumulation and DNA damage induced by L-NDDP and cisplatin in LoVo and LoVo/PDD cells. Our results indicate that the accumulation of L-NDDP in LoVo cells is several-fold higher than that of cisplatin; that the accumulation of L-NDDP is similar in both cell lines, whereas that of cisplatin is reduced by 2- to 3-fold in LoVo/PDD cells; and that the transmembrane transport of cisplatin is highly dependent on temperature while that of L-NDDP is not. We also found that the cytotoxicity of both agents correlates with the extent of DNA-protein cross-link formation, and that DNA interstrand cross-linking does not appear to play a role in the cytotoxicity of L-NDDP, whereas it correlates with cisplatin cytotoxicity.
脂质体顺式-双新癸酸根-反式-R,R-1,2-二氨基环己烷铂（II）（L-NDDP）是一种脂质体包裹的铂配合物，在人结肠癌LoVo细胞中显示出对顺铂部分缺乏交叉耐药性。我们研究了L-NDDP和顺铂在LoVo细胞及LoVo/PDD细胞中引起的药物蓄积和DNA损伤。我们的结果表明，L-NDDP在LoVo细胞中的蓄积比顺铂高几倍；L-NDDP在两种细胞系中的蓄积相似，而顺铂在LoVo/PDD细胞中的蓄积减少了2至3倍；顺铂的跨膜转运高度依赖温度，而L-NDDP则不依赖。我们还发现，两种药物的细胞毒性与DNA-蛋白质交联形成的程度相关，并且DNA链间交联似乎在L-NDDP的细胞毒性中不起作用，而它与顺铂的细胞毒性相关。
