Tumours from a cell strain with a high content of metallothionein show enhanced resistance against cis-dichlorodiammineplatinum.
Tumours from a cell strain with a high content of metallothionein show enhanced resistance against cis-dichlorodiammineplatinum.
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来自具有高含量金属硫蛋白的细胞株的肿瘤表现出对顺式二氯二氨铂增强的抵抗力。
DOI：
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
H. Rugstad
中科院分区：
文献类型：
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作者：
L. Endresen;L. Schjerven;H. Rugstad
具有极高含量的半胱氨酸蛋白金属硫蛋白(MT)的培养细胞以前被证明在暴露于其他致命剂量的顺式二氯二胺(cis-DDP)、氯氨丁苯或强的莫司汀时表现出耐药性，并且在这种处理后有相当大比例的细胞内药物与MT相关。为了研究这种体内保护机制，将抗顺-DDP的高MT突变的小鼠成纤维细胞系及其仅含微量MT的亲本敏感系的细胞注射到裸鼠皮下(每组24只动物)，比较顺铂治疗过程中肿瘤生长情况。治疗组于接种细胞后第12、26、33天分别静脉注射顺铂4 mg/kg或8 mg/kg，对照组注射生理盐水。8毫克/公斤的剂量几乎完全抑制了来自亲本细胞和富含MT的变种的肿瘤的生长。然而，在注射4 mg/kg顺式顺铂后，来自亲本细胞的肿瘤体积减少了约80%，而来自富MT细胞的肿瘤几乎完全耐药。这项研究首次提供了证据表明，金属硫蛋白对顺式顺铂毒性的保护作用也在体内肿瘤中起到了中介作用。
Cultured cells with a high content of the extremely cysteine-rich protein metallothionein (MT) have previously been shown to exhibit resistance when exposed to otherwise lethal doses of cis-dichlorodiammineplatinum (cis-DDP), chlorambucil or prednimustine, and to have a significant proportion of intracellular drug associated with MT after such treatment. In order to study this protective mechanism in vivo, cells from a MT-rich variant of a murine fibroblast line resistant to cis-DDP and its parent sensitive line with only trace amounts of MT, were injected subcutaneously into nude mice (24 animals in each group), and tumour growth was compared during cis-DDP treatment. Animals in the treatment groups received 3 intravenous doses of either 4 mg/kg or 8 mg/kg of cis-DDP on day 12, 26 and 33 after inoculation of cells, whereas the control groups received saline. The 8 mg/kg dose produced an almost complete growth inhibition of the tumours derived from the parent cells, as well as from the MT-rich variant. However, following the injections with 4 mg/kg of cis-DDP, tumour volume was reduced by approximately 80% in tumours from the parent cells, whereas the tumours from MT-rich cells were almost completely resistant. This study provides for the first time evidence that metallothionein-conferred protection against cis-DDP toxicity also is mediated in tumours in vivo.
金属硫蛋白作为反应性有机中间体的陷阱。
影响因子：
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作者：
Klaassen,CD;Cagen,SZ
通讯作者：
Cagen,SZ