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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 cells and the reversal of multidrug resistance in vitro, and to study the effect of liposomal formulations on the above-mentioned effects. Methods MTT assay was used to detect the cytotoxicity and multidrug resistance reversal effect of Ligustrazine liposome and Ligustrazine raw control group, blank liposome control group on human leukemia cell line (K562/ADM) resistant to doxorubicin. RESULTS Ligustrazine liposomes had obvious cytotoxic effects on K562/ADM. The non-cytotoxic dose (growth rate ≥95%) was 2.0 μg·ml-1, which significantly reduced the IC50 of ADM on K562/ADM cells (P<0.01), and the drug resistance reversal was 11.2 times. The low toxic dose (growth rate of 85-90%) was 2.6 μg·ml-1, and the drug resistance reversal was 178 times. The 0.2 μg·ml-1 Ligustrazine raw control group can significantly reduce the IC50 of ADM on K562/ADM cells (P<0.01), and the drug resistance reversal is 7.9-fold; the blank liposome control group diluted from the same period can significantly reduce the ADM The IC50 of K562/ADM cells (P<0.01) showed a 4.9-fold reversal of drug resistance. Conclusion Ligustrazine liposomes has significant cytotoxicity and MDR reversal effect on human leukemia cell K562/ADM in vitro; the cytotoxicity and reversal effect of Ligustrazine liposomes is dose-dependent in a certain concentration range; liposomes themselves Reversal has a synergistic effect.