Potentiation of cytotoxicity of Kaposi's sarcoma related to immunodeficiency syndrome (AIDS) by liposome-encapsulated doxorubicin.
Potentiation of cytotoxicity of Kaposi's sarcoma related to immunodeficiency syndrome (AIDS) by liposome-encapsulated doxorubicin.
复制标题
DOI：
10.1089/aid.1993.9.741
复制
发表时间：
1993-08
影响因子：
1.5
通讯作者：
R. Masood;S. R. Husain;Aquilur Rahman;P. Gill
中科院分区：
文献类型：
--
作者：
R. Masood;S. R. Husain;Aquilur Rahman;P. Gill
卡波西肉瘤是诊断艾滋病的独立标准，占所有病例的近15%。目前的化疗方案具有很大的毒性，特别是骨髓抑制，这限制了它们的长期使用。为了减少治疗相关的毒性并增强肿瘤细胞对药物的吸收，我们在体外对游离和脂质体包裹的阿霉素进行了测试。脂质体由心磷脂、磷脂酰胆碱和胆固醇制备。将卡波西肉瘤（KS）来源的梭形细胞暴露于游离多柔比星（DOX）和脂质体包裹的多柔比星（LED）不同时间间隔，分析细胞毒性、胸苷结合和细胞药物摄取。对游离DOX和LED的KS细胞的细胞毒性研究显示，IC50分别为288和7.5 ng/ml，因此LED的细胞毒性高38倍。胸苷在KS细胞中的掺入研究表明，与游离DOX相比，胸苷掺入对LED的毒性高出1倍以上。细胞药物摄取研究表明，在KS细胞中，游离DOX浓度在1小时内达到峰值，而LED持续积累至4小时。在4小时，通过LED的蒽环类药物摄取比游离药物摄取高5倍。同样，通过直接荧光显微镜评估的细胞中LED的摄取比游离药物的摄取更强烈和更频繁。因此，AIDS-KS细胞对LED非常敏感，这可能在临床应用中提供更高的治疗毒性指数。
Kaposi's sarcoma is an independent criterion for the diagnosis of AIDS and develops in nearly 15% of all cases. Current chemotherapy regimens are associated with substantial toxicity, particularly bone marrow suppression, which limit their long-term use. In an attempt to reduce treatment-related toxicity and enhance uptake of the drug in tumor cells, free and liposome-encapsulated doxorubicin was tested in vitro. The liposomes were prepared with cardiolipin, phosphatidylcholine, and cholesterol. Kaposi's sarcoma (KS)-derived spindle cells were exposed to free doxorubicin (DOX) and liposome-encapsulated doxorubicin (LED) for various time intervals and analyzed for cellular cytotoxicity, thymidine incorporation, and cellular drug uptake. Cytotoxicity studies of KS cells with free DOX and LED showed an IC50 of 288 and 7.5 ng/ml, respectively, hence demonstrating a 38-fold higher cytotoxicity by LED. Thymidine incorporation studies in KS cells demonstrated over one log higher toxicity to LED compared to free DOX. Cellular drug uptake studies showed that free DOX concentration peaked in 1 hr in KS cells whereas LED continued to accumulate up to 4 hr. At 4 hr, anthracycline uptake through LED was fivefold higher than the uptake of free drug. Similarly LED uptake in the cells evaluated by direct fluorescent microscopy was much more intense and more frequent than the uptake of free drug. Thus AIDS-KS cells appear to be exquisitely sensitive to LED, which may provide a higher therapeutic to toxicity index in clinical use.