Mirski S E, Gerlach J H, Cole S P
Cancer Res. 1987 May 15;47(10):2594-8.
A multidrug resistant variant (H69AR) of the human small cell lung cancer cell line NCI-H69 was obtained by culturing these cells in gradually increasing doses of Adriamycin up to 0.8 microM after a total of 14 months. H69AR expresses the multidrug resistant phenotype because it is cross-resistant to anthracycline analogues including daunomycin, epirubicin, menogaril, and mitoxantrone as well as to acivicin, etoposide, gramicidin D, colchicine, and the Vinca alkaloids, vincristine and vinblastine. H69AR is also similar to other multidrug resistant cell lines in that it displays little or no cross-resistance to bleomycin, 5-fluorouracil, and carboplatin. It has a slight collateral sensitivity to 1-dehydrotestosterone and lidocaine. H69AR has increased cell-cell adhesiveness compared to H69, but a similar growth rate in vitro and tumorigenicity in nude mice. When cultured in the absence of Adriamycin, there is a 40% decrease in resistance by 35 days of culture, compared to cells in continuous culture in drug, but no further decrease in resistance up to 181 days. Monoclonal antibodies to P-glycoprotein have no detectable reactivity with H69AR cells as determined by enzyme-linked immunosorbent assay and immunoblotting techniques. Thus, unlike most multidrug resistant cell lines, H69AR does not appear to express enhanced levels of P-glycoprotein. H69AR will provide a useful model for the study of multidrug resistance in human small cell lung cancer.
通过在总共14个月的时间里，用逐渐增加剂量的阿霉素（最高达0.8微摩尔）培养人小细胞肺癌细胞系NCI-H69，获得了一种多药耐药变体（H69AR）。H69AR表现出多药耐药表型，因为它对包括柔红霉素、表柔比星、美诺加里尔和米托蒽醌在内的蒽环类类似物以及阿西维辛、依托泊苷、短杆菌肽D、秋水仙碱和长春花生物碱长春新碱和长春碱具有交叉耐药性。H69AR对博来霉素、5-氟尿嘧啶和卡铂几乎没有或没有交叉耐药性，这一点也与其他多药耐药细胞系相似。它对1-脱氢睾酮和利多卡因有轻微的协同敏感性。与H69相比，H69AR的细胞间黏附性增加，但在体外的生长速率和在裸鼠中的致瘤性相似。在没有阿霉素的情况下培养时，与持续在药物中培养的细胞相比，培养35天时耐药性降低了40%，但在长达181天的时间里耐药性没有进一步降低。通过酶联免疫吸附测定和免疫印迹技术测定，针对P-糖蛋白的单克隆抗体与H69AR细胞没有可检测到的反应性。因此，与大多数多药耐药细胞系不同，H69AR似乎没有表达增强水平的P-糖蛋白。H69AR将为研究人类小细胞肺癌中的多药耐药性提供一个有用的模型。
