摘要
目的:研究洛美利嗪在高浓度、长时间作用于肿瘤细胞时,对多药耐药的逆转作用。探讨洛美利嗪逆转肿瘤细胞多药耐药的机制。方法:将不同浓度的洛美利嗪与人红白血病细胞系K562及其耐药细胞系K562/A02(耐阿霉素)共孵育24、48或72小时,然后分别向细胞中加入阿霉素,采用MTT法检测细胞毒作用;以流式细胞术测定两种细胞系内罗丹明123的潴留以反映P-糖蛋白的外排功能;利用Fluo-3/AM检测细胞内游离钙离子浓度。结果:细胞与洛美利嗪预温孵后,阿霉素对K562/A02细胞的IC50值减小,细胞内Rh123潴留增多,细胞内游离钙离子浓度明显升高。结论:洛美利嗪高浓度,长时间作用于K562/A02细胞,可以抑制细胞上P-糖蛋白的功能活性,使细胞对化疗药的敏感性增强,其机制可能与升高细胞内钙离子有关。
Objective： This experiment was to study the reversal effect of lomerizine on muhidrug resistance （MDR）in K562/A02 at high concentration and after long-time treatment, as well as to study its mechanism. Methods： After preincubating human leukemic cell line K562 and its multidrug resistant counterpart K562/A02 cells with lomerizine for 24, 48 or 72 hours, ADM was added. Cytotoxicity was evaluated by MTT assay, intracellular Rh123 retention was measured by flow cytometry, and cellular [Ca^2＋ ]i was measured by fluo-3/ AM. Results. K562/A02 cells reduced Rh123 retention compared to their parental K562 cells. Lomerizine could diminish the IC50 value of ADM to K562/A02, increase Rh123 retention and cellular [Ca^2＋ ]i in K562/A02 cells after preincubation. Conclusion： Lomerizine could reverse the MDR in K562/A02 cells by inhibiting the functional activity of P-gp and increasing the chemosensibility of K562/A02 to ADM at high concentration and after long-time treatment. The reversal mechanism may be through increasing cellular [ Ca^2＋ ]i.
出处
《药学进展》
CAS
2006年第9期413-417,共5页
Progress in Pharmaceutical Sciences
