中文摘要：

目的：探讨哌啶生物碱洛贝林对人乳腺癌多药耐药细胞株MCF-7/ADM耐药的逆转作用及其分子机制。方法：利用MTT比色法测定不同浓度洛贝林对人乳腺癌细胞株MCF-7/ADM的阿霉素（ADM）和氟尿嘧啶（Fu）的耐药逆转指数。多功能酶标仪测定洛贝林干预对细胞内罗丹明123荧光强度以反映其对细胞多药耐药蛋白P-gp活性的影响。同时用流式细胞术检测洛贝林对MCF-7/ADM细胞内罗丹明123积聚浓度的影响,从功能学的角度观察洛贝林的耐药逆转作用及其机制。结果：洛贝林（10μmol/L）干预下,多药耐药细胞株MCF-7/ADM对化疗药的敏感性增加,ADM对耐药细胞株的IC50由（44.81±0.43）mg/L降至（16.72±0.75）mg/L,逆转指数为2.68;Fu对耐药细胞株的IC50由（53.12±1.60）mg/L降至（38.90±1.43）mg/L,逆转指数为1.37。洛贝林对细胞的罗丹明123外排有显著的浓度依赖性抑制作用。洛贝林（20μmol/L）的多药耐药逆转有效率为经典耐药逆转剂维拉帕米（20μmol/L）的71.6%,但毒副作用显著降低。结论：洛贝林对乳腺癌多药耐药细胞株MCF-7/ADM的耐药性具有逆转作用,其机制主要为抑制细胞多药耐药蛋白P-gp的活性。

英文摘要：

Objective To explore the reversal effect and mechanism of lobeline on the multidrug-resistance（MDR） of human breast cancer cells MCF-7/ADM.Methods In human breast cancer cell line MCF-7/ADM,MTT assay was used to determine the cell growth inhibiting ratio of MCF-7/ADM by ADM and Fu.Fluorospectorphotometer was employed to investigate the intracellular concentration of rhodamine123 to reflect the effect of lobeline on the activity of MDR-related protein P-glycoprotein（P-gp）.Taking untreated MCF-7/ADM cells as controls,flow cytometry was applied to detect the intracellular concentration of rhodamine123 in MCF-7/ADM cell intervened with lobeline of 20 μmol/L.Results The sensitivity of MCF-7/ADM to ADM and Fu was significantly increased by lobeline in a dose-dependent manner.The inhibitive concentration 50（IC50） of ADM declined from（44.81±0.43） mg/L to（16.72±0.75） mg/L with a reversion index of 2.68.The IC50 of Fu declined from（53.12±1.60） mg/L to（38.90±1.43） mg/L with a reversion index of 1.37.The fluorescence intensity of lobeline-treated cells was significantly higher than that of the controls,when the concentration of lobeline was more than 10 μmol/L.With fewer side effects,the reversal efficacy of 20 μmol/L lobeline was 71.6% of the classical MDR reversal agent of verapamil at the same concentration.Conclusion Lobeline can reverse the MDR of MCF-7/ADM cells by inhibiting the activity of P-glycoprotein.