Chauffert B, Martin M, Hammann A, Michel M F, Martin F
Cancer Res. 1986 Feb;46(2):825-30.
The mechanisms of the resistance of intestinal cancer to anthracyclines were studied on an experimental model of rat colon cancer cells. The accumulation of anthracyclines in the nucleus of living cancer cells was observed by fluorescence microscopy. This accumulation depended on both the capacity of anthracyclines to penetrate into the cell and the activity of an efflux mechanism extruding the drug from the cell. We found that 4'-deoxydoxorubicin was superior to 4 other anthracyclines in its capacity to penetrate into confluent colon cancer cells. Amiodarone, an antiarrhythmic agent used in cardiology, inhibited the efflux mechanism efficiently and increased the toxicity of anthracyclines to the colon cancer cells. Association of amiodarone and 4'-deoxydoxorubicin was able to cure 5 of 13 rats that had been inoculated i.p. previously with syngeneic colon cancer cells. This association could be of interest in the treatment of human colon cancer.
在大鼠结肠癌细胞实验模型上研究了结肠癌对蒽环类药物耐药的机制。通过荧光显微镜观察蒽环类药物在活癌细胞核中的蓄积情况。这种蓄积既取决于蒽环类药物进入细胞的能力，也取决于将药物排出细胞的外排机制的活性。我们发现4'-脱氧阿霉素在进入汇合的结肠癌细胞的能力方面优于其他4种蒽环类药物。胺碘酮，一种用于心脏病学的抗心律失常药物，能有效抑制外排机制并增加蒽环类药物对结肠癌细胞的毒性。胺碘酮与4'-脱氧阿霉素联合使用能够治愈13只先前经腹腔接种同基因结肠癌细胞的大鼠中的5只。这种联合用药可能对人类结肠癌的治疗有意义。
