Zhu Hao-jie, Wu Yu-lin, Liu Guo-qing
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2004 May;39(5):333-7.
To study the effect of lomerizine (Lom) on the reversal of multidrug resistance (MDR) in K562/ADM cells and its mechanism.
MTT assay was used to determine the influence of Lom on the cytotoxicity of adriamycin (ADM). The effect of Lom on the apoptosis induced by ADM and vincristine (VCR) in K562/ADM cells was detected using flow cytometry. Intracellular accumulation of ADM was measured by fluorescence spectrophotometry. Flow cytometry was used to investigate the efflux of rhodamine 123 (Rh123) and the expression of P-glycoprotein (P-gp) in K562/ADM cells.
Lom increased the cytotoxicity of ADM and the apoptosis induced by ADM or VCR in K562/ADM cells. At the concentration of 3, 10 and 30 micromol x L(-1), Lom reduced the IC50 value of ADM from 79.03 micromol x L(-1) to 28.14, 8.16 and 3.16 micromol x L(-1), respectively. Lom increased the intracellular accumulation of ADM and inhibited the efflux of Rh123 in K562/ ADM cells. No change in P-gp expression was observed after the treatment of Lom for 72 h.
Lom had strong reversal effect on MDR in K562/ADM cells by inhibiting P-gp function.
研究洛美利嗪（Lom）对K562/ADM细胞多药耐药（MDR）的逆转作用及其机制。
采用MTT法测定Lom对阿霉素（ADM）细胞毒性的影响。采用流式细胞术检测Lom对ADM和长春新碱（VCR）诱导K562/ADM细胞凋亡的影响。用荧光分光光度法测定细胞内ADM的蓄积量。采用流式细胞术研究罗丹明123（Rh123）的外排及K562/ADM细胞中P-糖蛋白（P-gp）的表达。
Lom增加了ADM的细胞毒性以及ADM或VCR诱导的K562/ADM细胞凋亡。在3、10和30 μmol·L⁻¹浓度下，Lom分别将ADM的半数抑制浓度（IC50）值从79.03 μmol·L⁻¹降至28.14、8.16和3.16 μmol·L⁻¹。Lom增加了K562/ADM细胞内ADM的蓄积并抑制了Rh123的外排。Lom处理72小时后，未观察到P-gp表达的变化。
Lom通过抑制P-gp功能对K562/ADM细胞的MDR具有较强的逆转作用。
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