Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles.
Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles.
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发表时间：
2003-08
期刊：
影响因子：
11.2
通讯作者：
K. Shedden;Xuesun Xie;Parthapratim Chandaroy;Young‐Tae Chang;G. Rosania
中科院分区：
文献类型：
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作者：
K. Shedden;Xuesun Xie;Parthapratim Chandaroy;Young‐Tae Chang;G. Rosania
抗癌药物耐药性来自化疗的选择性压力，以及使细胞难以治疗的突变或表观遗传变化。在癌细胞中，我们报告说，基因表达相关的小泡脱落与化疗敏感性档案。多柔比星和其他小分子的实验证实了药物在脱落囊泡中的积聚和排出。囊泡脱落率的相对差异与不同细胞系的阿霉素耐药性相对应。此外，药物在囊泡起源的膜结构域中的积累解释了脱落囊泡中的药物排出。这些观察结果暗示囊泡脱落作为药物外排机制可能涉及耐药性。
Anticancer drug resistance results from selective pressure of chemotherapy, together with mutations or epigenetic changes that make cells refractory to treatment. In cancer cells, we report that gene expression associated with vesicle shedding correlates with chemosensitivity profiles. Experiments with doxorubicin and other small molecules confirm drug accumulation and expulsion in shed vesicles. Relative differences in the rate of vesicle shedding correspond with doxorubicin resistance across various cell lines. Moreover, accumulation of drug in membrane domains in which vesicles originate accounts for drug expulsion in shed vesicles. These observations implicate vesicle shedding as a drug efflux mechanism potentially involved in drug resistance.