人卵巢癌细胞阿霉素耐药株的建立及其耐药机制的研究  

Establishing a new adriamycin-resistant cell line and studying its mechanism of drug resistance.

作　　者：黄薇[1] 李力[1] 唐东平 陈心秋 黎丹戎 

机构地区：[1]广西医科大学附属肿瘤医院

出　　处：《现代妇产科进展》1998年第1期4-7,共4页Progress in Obstetrics and Gynecology

摘　　要：目的：建立人卵巢癌体外耐药模型，研究卵巢癌对阿霉素的耐药特征和机制。万法；应用浓度递增和短时间作用法，从人卵巢癌细胞A2780中培养出对阿霉素耐药细胞亚株（A2780／ADM）。采用MTT法检测耐药细胞的耐药指数及对抗癌药物的敏感性，用高效液相色谱仪捡测耐药细胞内阿霉素含量，以及应用RT-PCR法和免疫组化法检测MDR1和GST－π的表达情况。结果：（1）A2780／ADM对ADM的耐药指数为38．2，而且其倍增时间较A2780细胞延长，对VCR、MTX呈高度耐药状态，对KSM、CARP、PYM、VP16、CTX和5－FU均有不同程度的耐药。（2）耐药细胞内阿霉素含量明显低于A2780细胞。（3）耐药细胞MDR1的表达呈阳性，而GST－π只有在高浓度的耐药细胞内才呈弱阳性。结论：A2780细胞对阿霉素的耐药是获得性的，并呈多药耐药特征，其耐药的主要原因是细胞内MDR1的过度表达，导致药物在耐药细胞内浓度降低。此项研究结果有助于卵巢癌患者化疗选用药物时作为参考。To establish a new adriamycin (ADM)-resistant cell line of humanovarian cancer and to investigate its features and resistant mechanism to ADM. Methods: A ADM-resistant human ovarian cancer cell line (A2780/ADM ) was induced by gradually increasing concentrations of ADM and short-time action with ADM. The resistance and the sensitivity of the anticancer drugs were screened in the A2780/ADM by MTT method.ADM content in the A2780/ADM was detected by high-performance liquid chromatography (HPLC ). The reverse transcription polymerase chain reaction (RT-PCR ) and the immunohistochemical method were used to measure multidrug resistance gene 1 (MDR1)and glutathione-S-transferase-π (GST-π ). Results: (1) A2780/ADM cells were of 38. 2-fold resistance to ADM and displayed high resistance to ADM, VCR, MTX , but low variable resistance to KSM, cARP , PYM, VP16, CTX and 5 -FU. As compared to A2780 cells, the double time of A2780/ADM cells was significantly longer. (2)ADM content of foe A2780/ ADM cells decreased significantly. (3)There was higher overexpression of MDR1 and lower expression of GST-π in A2780/ADM cells. Conclusions: The resistance of A 2780/ADM cells to ADM is acquired and has a character of multidrug resistance. The main machanism causing A2780/ADM cells resistant to ADM is overexpression of MDR, and the reducing intracellular content of ADM. The study may be helpful for selecting drugs of chemotherapy for patients with ovarian cancer.

关 键 词：卵巢肿瘤 阿霉素 药物耐受性 细胞株 耐药株 

分 类 号：R737.310.5[医药卫生—肿瘤]