THE DEVELOPMENT OF DRUG-RESISTANCE BY TUMOR-CELLS IN-VITRO IS ACCOMPANIED BY THE DEVELOPMENT OF SENSITIVITY TO SELENITE
THE DEVELOPMENT OF DRUG-RESISTANCE BY TUMOR-CELLS IN-VITRO IS ACCOMPANIED BY THE DEVELOPMENT OF SENSITIVITY TO SELENITE
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DOI：
10.1016/0304-3835(94)90165-1
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发表时间：
1994-06-15
期刊：
影响因子：
9.7
通讯作者：
FRENKEL, GD
中科院分区：
文献类型：
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作者：
CAFFREY, PB;FRENKEL, GD
将亚硒酸盐对药物敏感的人卵巢肿瘤（A2780）细胞系中的细胞存活力和增殖的作用与其对这些细胞（A2780-ME）的体外开发的美法仑抗性衍生物的作用进行比较（汉密尔顿等人（1985）生化药理学，34，2583-2586）。对于A2780-ME细胞，在暴露于小于100 μ M亚硒酸盐6小时后，活细胞（即排除台盼蓝染料）的数量减少50%。与此相反，暴露于300 μ M以上的亚硒酸盐，需要达到相同的效果，在亲系。同样，暴露于10 μ M亚硒酸盐导致A2780-ME细胞增殖减少50%，而这种治疗对亲本细胞的增殖只有很小的抑制作用。因此，体外美法仑抗性的发展伴随着亚硒酸盐敏感性的发展。预暴露的两种类型的细胞buthiflavine亚砜亚胺消除了他们的细胞内谷胱甘肽水平的差异，以及他们的大部分差异敏感性亚硒酸盐。此外，这两种细胞类型没有表现出对亚硒酸盐与谷胱甘肽反应的产物selenodigtuture的敏感性的差异。因此，细胞内谷胱甘肽的增加，这已被证明是负责在这些细胞中的耐药性的发展也负责亚硒酸盐敏感性的发展。
The effects of selenite on cell viability and proliferation in a line of drug-sensitive human ovarian tumor (A2780) cells were compared with its effects on a melphalan-resistant derivative of these cells (A2780-ME) which had been developed in vitro (Hamilton et al. (1985) Biochemical Pharmacol., 34, 2583-2586). With the A2780-ME cells there was a 50% decrease in the number of viable cells (i.e. which exclude Trypan Blue dye) after exposure to less than 100 mu M selenite for 6 h. In contrast, exposure to more than 300 mu M selenite was required to achieve the same effect in the parent line. Similarly, exposure to 10 mu M selenite resulted in a 50% decrease in A2780-ME cell proliferation, whereas this treatment had only a small inhibitory effect on proliferation of the parent cells. Thus, the development of melphalan resistance in vitro was accompanied by the development of selenite sensitivity. Pre-exposure of the two cell types to buthionine sulfoximine eliminated the difference in their intracellular glutathione levels, as well as most of their differential sensitivity to selenite. Furthermore, the two cell types did not exhibit a difference in sensitivity to selenodigtutathione, the product of the reaction of selenite with glutathione. Thus, the increase in intracellular glutathione, which has been shown to be responsible for the development of drug resistance in these cells is also responsible for the development of selenite sensitivity.