Kimura I, Ohnoshi T, Hiraki S, Miyamoto H
Gan To Kagaku Ryoho. 1987 Mar;14(3 Pt 2):830-6.
An adriamycin-resistant cell line was established in culture by continuous exposure of SBC-3 cells, a cell line of human small-cell lung cancer, to increasing concentrations of adriamycin, followed by a cloning procedure. The resistant cells (SBC-3/ADM) were 30 times more resistant to the drug than the parent cells in terms of 70% lethal dose, determined by soft agar clonogenic assay. Uptake studies using [3H] daunomycin, which was completely cross-resistant to adriamycin, showed decreased influx and enhanced efflux of the agent. This resistance to adriamycin may be attributed to an alteration in membrane transport, resulting in reduced intracellular accumulation of the drug. Using the SBC-3/ADM cells, the activity of a variety of drugs was analyzed by soft agar clonogenic assay in order to search for a means of circumventing drug resistance. The SBC-3/ADM cells were markedly resistant to anthracycline antibiotics such as THP-adriamycin and 4'-epi-adriamycin. The cells were also resistant to structurally or pharmacodynamically unrelated compounds such as vincristine, mitomycin C, 40497S, an active compound of ifosfamide, and etoposide. However, the cells were as sensitive to mitoxantrone as the parent cells, and were considerably susceptible to cisplatin. These results suggest that mitoxantrone and cisplatin may exert a sufficient degree of activity for use against small-cell lung cancer resistant to adriamycin.
通过将人小细胞肺癌细胞系SBC - 3细胞持续暴露于浓度递增的阿霉素中，随后进行克隆程序，在培养中建立了阿霉素耐药细胞系。通过软琼脂克隆形成试验测定，在70%致死剂量方面，耐药细胞（SBC - 3/ADM）对该药物的耐药性是亲本细胞的30倍。使用对阿霉素完全交叉耐药的[3H]柔红霉素进行摄取研究，结果显示该药物的流入减少而流出增强。这种对阿霉素的耐药性可能归因于膜转运的改变，导致药物在细胞内的积累减少。使用SBC - 3/ADM细胞，通过软琼脂克隆形成试验分析了多种药物的活性，以寻找克服耐药性的方法。SBC - 3/ADM细胞对诸如THP - 阿霉素和4'-表阿霉素等蒽环类抗生素具有明显的耐药性。这些细胞对结构或药效学无关的化合物如长春新碱、丝裂霉素C、异环磷酰胺的活性化合物40497S和依托泊苷也具有耐药性。然而，这些细胞对米托蒽醌的敏感性与亲本细胞相同，并且对顺铂相当敏感。这些结果表明，米托蒽醌和顺铂可能对阿霉素耐药的小细胞肺癌具有足够的活性。
