The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo.
The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo.
复制标题
维拉帕米和硫帕米类似物 DMDP 对 P388 阿霉素耐药和敏感白血病中阿霉素诱导的体外和体内细胞毒性的影响。
DOI：
10.1007/bf00262733
复制
发表时间：
1988
影响因子：
3
通讯作者：
Rustum,YM
中科院分区：
文献类型：
--
作者：
Radel,S;Bankusli,I;Mayhew,E;Rustum,YM
DMDP [N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-napthyl)-m-dithane-2-propylamine] a recently developed calcium antagonist analogue, caused a greatly increased intracellular retention of adriamycin and concomitant enhanced cytotoxicity in adriamycin-resistant P388 leukemia cells in vitro. These effects of DMDP were greater than those of another calcium channel blocker, verapamil, and occurred at one-half the dosage levels. Only slight enhancement in adriamycin toxicity was observed for either of these agents in the adriamycin-sensitive parental cell line. However, no significant therapeutic potentiation of adriamycin activity occurred with either verapamil or DMDP treatment in vivo. In vivo maximum DMDP tumor intracellular concentrations, as analyzed by HPLC, were the same in vitro tumor cell levels required to overcome adriamycin resistance. This inability to overcome drug resistance in vivo at acceptable levels of host toxicity is not only a function of maintaining necessary calcium antagonist concentrations in resistant tumor cells.
