摘要
急性白血病细胞对化疗药耐药性是化疗失败的主要原因,在本研究中应用新的钙调素拮抗剂0-4-乙氧基-丁基-小檗胺(0-4-ethoxy-butyl-berbamine,EBB)体外逆转多药耐药性获得成功。EBB对多药耐药K562/VCR细胞系具有抑制作用并有剂量依赖关系,低浓度的EBB(IC10 0.35μg/ml)与长春新碱联合应用可提高长春新碱对细胞的毒性作用,其IC50由1.89μg/ml降至0.37μg/ml;K562/VCR细胞系对EBB的敏感性明显高于K562细胞,用斑点杂交的方法证明EBB可降低MDR-1的mRNA表达;用免疫荧光方法证明EBB可降低p170蛋白在K562/VCR细胞中的表达,其阳性率由42％降至5.9％;电镜观察显示EBB作用后的K562/VCR细胞中高尔基区比对照组小;用流式细胞仪测定单个细胞DNA水平,证明EBB增加细胞在G_2/M期的百分比(EBB组为39％,对照组为22％)。以上结果证明EBB可能是一个有前途的耐药逆转剂,并具有多种逆转耐药途径。
Drug - resistance to chemotherapeutic agent is a common cause of treatment failure for acute leukemia. This work showed reversai of multidrug resistance using a new calmodulin antagonist EBB (0 - 4 - ethoxy - butyl - berbamine) is successful in vitro.
EBB possesses inhibitory effect on multidrug resistance K562/VCR celi line with dose - dependent relationship. EBB with low concentration (IC10 0.35 μg/ml) in combination with vincristine en-hanced the cytotoxic effect of vincristine, its IC50 value decreased from 1. 89μg/ml to 0. 37 μg/ml. Sensitivity of K562/VCR cells to EBB is higher than K562 cells significantly.
EBB may decrease MDR- 1 mRNA expression by dot blotting and p170 glycoprotein level by im-munofluorescent assay in K562/VCR celi line, its positive rate is reduced from 42% to 5. 9% . Electron microscopic observation revealed that the size of Golgi complex in K562/VCR celis in the presence of EBB is smaller compared with that in control. Flow cytometry studies on singe cell DNA levels indi-cated that EBB had enhanced cellular accumulation and retention in G2/M phase (39% in the EBB treated group but 22 % in the control group).
This result confirmed that EBB is possibly a kind of prospective agent for reversai of multidrug resistance and different mechanisms existed in reversai of drug- resistance in K562/VCR cell line.
出处
《中国实验血液学杂志》
CAS
CSCD
1996年第3期294-298,共5页
Journal of Experimental Hematology
基金
天津市自然科学基金 编号 934009019
