摘要
本文用3株体外培养的细胞研究了钙拮抗剂戊脉安对安吖啶细胞毒的增效作用。台盼蓝拒染实验表明,0.5、2及10μg/ml 戊脉安处理48h 并不能增加 P_(388)细胞的蓝染细胞百分率,而与安吖啶合用时却可以明显增加安吖啶(0.01～0.39μg/ml)处理后 P_(388)细胞的蓝染百分率,拒染细胞下降幅度随着安吖啶浓度的增加而加大,其百分率下降曲线为双相性。在 P_(388)及 HEP-3细胞中双层琼脂或普通平皿法测定的克隆形成细胞活存率实验也证实了戊脉安有相同的增效作用。将上述结果与用有效率乘积法计算的两药作用相加的理论值进行比较时发现,实验结果明显超过理论值,提示两药合用时有“超相加”作用。文章还应用离心淘洗法分离了 V_(79)细胞的 G_1、S 及 G_2M 时相细胞,并研究了两药合用时细胞毒的时相特异性,结果表明安吖啶细胞毒作用存在明显时相特异性,以 G_2M 细胞敏感性最高,S 细胞次之,G_1细胞敏感性最低。戊脉安对安吖啶细胞毒的增效作用也存在明显的时相特异性,其中对 G_2M 及 S 细胞的增效幅度最大,对 G_1细胞的增效作用较弱。本文对其可能的临床意义进行了探讨。
The potentiation of amsacrine (AMSA) cytotoxicity by verapamil (VER) was investiga- ted in three cell lines in vitro.Trypan blue exclusion test showed that no blue-stained cells could be found in P_(388) cells treated with VER 0.5,2,or 10μg/ml alone.When the P_(388) cells were treated by VER-AMSA combination the percentage of the AMSA-induced blue-stained cells increased significantly.The survival curve of the viable cells (dye-excluded) following drug treatment was biphasic.Clonogenic cell survival assay in P_(388) and HEP-3 cells treated by AMSA alone or in combination with VER revealed similar enhancement effect of VER on AMSA cytotoxicity.In comparison with the theoretical value calculated by the Webb's fractional product equation of two drugs the experimental results were much higher than ex- pected.It suggested that supra-additivity of cell-killing could be obtained following the VER- AMSA combination treatment.The cell-phase specific cytotoxicity of VER and AMSA was investigated in synchronized G_1,S,and G_2M V_(79) cells by centrifugal elutriation.It showed that the cytotoxicity of AMSA was phase-dependent,the most sensitive V_(79) cells were G_2M cells,with S cells intermediate,the G_1 cells were relatively resistant.VER possessed selective enhancement of the cytotoxicity of AMSA,with the most significant enhancement in G_2M and S cells and the least enhancement in G_1 cells.
出处
《军事医学科学院院刊》
CSCD
北大核心
1990年第2期109-114,共6页
Bulletin of the Academy of Military Medical Sciences
基金
国家自然科学基金资助项目
关键词
安吖啶
戊脉安
离心淘洗法
verapamil
amsacrine
centrifugal elutriation
