延长洛美利嗪作用时间可增加K562/A02细胞对阿霉素的敏感性

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。

Prolonging Treatment with Lomerizine May Increase Chemosensitivity of K562/A02 to Adriamycin

Objective: This experiment was to study the reversal effect of lomerizine on multidrug 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 IC_ 50 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 .