中文摘要：

目的：探寻大环内酯类药物多拉菌素逆转人乳腺癌多药耐药细胞株（MCF-7／adr）多药耐药（multidrugresistance，MDR）的作用及机制。方法：采用MTT比色法测定细胞生长抑制率及逆转倍数；高效液相色谱（HPLC）法检测细胞内阿霉素（ADR）的积累变化；荧光分光光度仪检测罗丹明123（Rhl23）在肿瘤细胞内的积累与外排；通过RT-PCR与流式细胞仪检测MDRl基因与P-糖蛋白（P-gp）表达的变化。结果：5μmol·L-1的多拉菌素可明显增强MCF-7／adr对ADR的敏感性，逆转倍数可达28．93，并增强了细胞内ADR及Rhl23的积累，呈剂量依赖关系。同时，MDRl及P-gp的表达降低。结论：多拉菌素对MCF-7／adr的耐药有一定的逆转作用，有希望成为肿瘤多药耐药的逆转剂。

英文摘要：

OBJECtIVE To explore the reversal effects of macrocyclic lactone antibiotics doramectin on MDR in adriamycin- resistant human breast carcinoma cells （MCF-7/adr）. METHODS The MTT assay was used to evaluate the cell suppression rates and reversal effects. Intracellular accumulation of adriamycin was determined by HPLC. The accumulation and efflux of rhodamine 123 （Rh123） was measured with spectrofluorometer. The expressions of P-gp and the MDRI gene encoding P-gp were tested by flow cytometry and reverse-transcriptase PCR. RESULTS Doramectin at the high dose of 5 /~mol-L-1 signifi- cantly increased the sensitivity of MCF-7/adr ceils to adriamycin by 28. 93-fold. Doramectin also increased the intracellular ac- cumulation of adriamycin and Rh123 in MCF-7/adr cells in a dose-dependent manner, and inhibited the efflux of rhodamine 123. Expression of both P gp and MDR1 were down-regulated. CONCLUSION Doramectin can partly reverse multidrug resist- ance of MCF-7/adr cells. Doramectin was more potent agent for overcoming MDR in cancer therapy.