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目的 探讨阿霉素对裸小鼠原位移植人肝癌多药耐药性的影响 ,并研究其耐药机制。方法 人肝癌 (BEL 740 2 )裸小鼠原位移植 ,用阿霉素腹腔注射诱导耐药 ,经MTT法检测原代培养的耐药细胞对抗癌药的敏感性 ,以流式细胞仪检测癌细胞表面mdr1基因产物P170的表达及功能。以裸小鼠原位移植人肝癌模型观察阿霉素对耐药组的疗效。结果 移植瘤组织形态及生物学方面符合人肝癌特征 ,耐药细胞表面P170表达为 75 45 %± 5 6 7% ,而对照组表达仅 4 2 5 %± 1 2 8% (P <0 0 1) ,对阿霉素的耐药倍数提高了 16 7倍 ,对羟基喜树碱和表阿霉素具有交叉耐受性(13 7倍和 7 5倍 )。耐药细胞表面P170有较强的药物外排功能。诱导后的肝癌在体内对阿霉素获得了明显的抗性。结论 阿霉素较易诱导原位移植于裸小鼠的人肝癌多药耐药性的产生 ,耐药机制主要与P170的过度表达有关
Objective To investigate the effect of doxorubicin on multidrug resistance of orthotopically transplanted human hepatocellular carcinoma (HCC) in nude mice and to study its drug resistance mechanism. Methods Human hepatocellular carcinoma (BEL 740 2 ) was implanted orthotopically in nude mice. Drug resistance was induced by intraperitoneal injection of adriamycin. The sensitivity of primary cultured drug-resistant cells to anticancer drugs was detected by MTT assay and detected by flow cytometry. Expression and function of mdr1 gene product P170 on the surface of cancer cells. The effect of adriamycin on drug resistance was observed in nude mice orthotopically transplanted with human hepatocellular carcinoma. Results The morphology and biological characteristics of the transplanted tumors were consistent with the features of human liver cancer. The expression of P170 on the surface of drug-resistant cells was 7545 % ± 56.7%, while that of the control group was only 4 25% ± 12.8% (P <0 0 1 ) The resistance to adriamycin was increased by a factor of 16 7 and cross-tolerance to hydroxycamptothecin and epirubicin (13 7-fold and 75-fold). P170 on the surface of drug-resistant cells has a strong drug efflux function. After induction, hepatocarcinoma obtained significant resistance to adriamycin in vivo. Conclusion Doxorubicin is more likely to induce the development of multidrug resistance in human hepatocellular carcinoma after orthotopic transplantation in nude mice. The mechanism of drug resistance is mainly related to overexpression of P170.