川芎嗪脂质体对人白血病细胞株K_(562)多药耐药逆转作用的研究

Study on Effect Reversing MDR of Ligustrazine Liposomes on Human Erythroleukemia cell line K _(562) /ADM

目的研究川芎嗪脂质体在体外对肿瘤细胞的细胞毒作用和对多药耐药的逆转作用,并研究脂质体剂型对上述作用的影响。方法MTT法检测川芎嗪脂质体以及川芎嗪原料对照组、空白脂质体对照组对耐阿霉素的人白血病细胞株(K562/ADM)的细胞毒性和多药耐药逆转作用。结果川芎嗪脂质体对K562/ADM有明显的细胞毒作用。非细胞毒性剂量(生长率≥95%)为2.0μg·ml-1,该浓度下可显著降低ADM对K562/ADM细胞的IC50(P<0.01),抗药性逆转为11.2倍。低毒剂量(生长率85～90%)为2.6μg·ml-1,抗药性逆转为178倍。2.0μg·ml-1的川芎嗪原料对照组可显著降低ADM对K562/ADM细胞的IC50(P<0.01),抗药性逆转为7.9倍;同比稀释的空白脂质体对照组可显著降低ADM对K562/ADM细胞的IC50(P<0.01),抗药性逆转为4.9倍。结论川芎嗪脂质体体外对人白血病细胞K562/ADM有明显的细胞毒作用和MDR逆转作用;在一定浓度范围内川芎嗪脂质体的细胞毒性与逆转作用有剂量依赖性;脂质体本身对逆转有增效作用。

Objective: To study the cytotoxic effect of ligustrazine liposomes on tumor cell in vitro and the reversing effect on the MDR , and explore the influence of dosage form on the above effects.Method: The MTT method was used to test cytotoxicity of liposomes and reverse of MDR in human erythroleukemia cell line K 562 /ADM. Two controlled groups, ligustrazine ingredient group and empty liposomes group, were established. Result: An obvious cytotoxicity to K 562 /ADM was observed in ligustrazine liposomes . No cell toxic dosage (growth rate≥ 95% ) of ligustrazine liposomes was 2.0 μg·ml -1 , which could significantly lower the IC 50 of K 562 /ADM by ADM( P < 0.01 ) and reverse MDR up to 11.2 times. Low toxic dosage (growth rate was 85%～95% ) was 2.6 μg·ml -1 , which could reverse MDR up to 178 times. Controlled groups: Ligustrazine ingredient ( 2.0 μg·ml -1 ) significantly lowered the IC 50 of K 562 /ADM by ADM ( P < 0.01 ) and reversed MDR 7.9 times. Iso ratio attenuant empty liposomes could significantly up to lower the IC 50 of K 562 /ADM by ADM ( P < 0.01 ) and revers MDR up to 4.9 times.Conclusion: 1) Ligustrazine liposomes has the cytotoxicity and effect reversing MDR in human erythroleukemia cell line K 562 /ADM. 2) In a certain range of concentrations, the cytotoxicity and reversing effect of liposomes are dependent on dosage. 3) The effect reversing MDR could be increased by the self liposomes.