O'Keeffe Joseph, Doyle Sean, Kavanagh Kevin
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
J Pharm Pharmacol. 2003 Dec;55(12):1629-33. doi: 10.1211/0022357022359.
Cancer patients experience a high incidence of fungal infections due to their immuno-suppressed condition. This work has investigated the interaction of an anti-neoplastic agent, adriamycin (doxorubicin), with the yeast Candida albicans and examined whether this drug altered the susceptibility of the yeast to amphotericin B - an anti-fungal agent used for the treatment of systemic fungal infections in cancer patients. Exposure to adriamycin for 24h increased the growth of C. albicans and increased the tolerance to amphotericin B by a small, but statistically significant, extent. Growth in adriamycin-supplemented medium suppressed the respiration rate of C. albicans, which resulted in a decrease in the ergosterol content of the fungal cell membrane. The tolerance to amphotericin B was lost after exposure to adriamycin for 48 h, which coincided with a restoration in the respiration rate and the ergosterol content of the fungal cell membrane. This work demonstrated that short-term exposure (24 h) to adriamycin increased the tolerance of C. albicans for amphotericin B, which may be mediated by a decrease in the ergosterol content as a result of an adriamycin-induced disruption of oxidative phosphorylation.
癌症患者由于免疫抑制状态，真菌感染的发生率很高。这项研究调查了一种抗肿瘤药物阿霉素（多柔比星）与白色念珠菌之间的相互作用，并研究了这种药物是否会改变该酵母对两性霉素B的敏感性，两性霉素B是一种用于治疗癌症患者系统性真菌感染的抗真菌药物。暴露于阿霉素24小时可增加白色念珠菌的生长，并在一定程度上（虽小但具有统计学意义）提高其对两性霉素B的耐受性。在添加阿霉素的培养基中生长会抑制白色念珠菌的呼吸速率，导致真菌细胞膜中麦角固醇含量降低。暴露于阿霉素48小时后，对两性霉素B的耐受性丧失，这与真菌细胞膜呼吸速率和麦角固醇含量的恢复相一致。这项研究表明，短期（24小时）暴露于阿霉素可增加白色念珠菌对两性霉素B的耐受性，这可能是由于阿霉素诱导的氧化磷酸化破坏导致麦角固醇含量降低所致。
