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通过增强阿霉素细胞毒性并降低培养基中谷氨酰胺或天冬酰胺水平来抑制培养的白血病细胞生长。

Inhibition of cultured leukemia cell growth by enhanced adriamycin cytotoxicity with reduction of glutamine or asparagine level in medium.

作者信息

Sukemori S, Sugimura K

机构信息

Rokkou Bio-Scientific Research Laboratory Co., Ltd., Saitama.

出版信息

Cancer Biochem Biophys. 1994 Sep;14(2):99-105.

PMID:7889497
Abstract

The effect of a singular amino acid, asparagine (Asn), glutamine (Gln), or proline deletion in a cultured medium (RPMI 1640 supplemented with 10% fetal calf serum and other ingredients) on adriamycin (ADR) cytotoxicity was evaluated in the growth of P388 murine leukemia cells and CEM human acute lymphoblastic leukemia cells over a 3 day period. No enhancement of ADR cytotoxicity was observed in the assay of IC50 values under the amino acid deleted condition. Singular deletion of Gln or Asn from ADR-free medium apparently inhibited the proliferation of both cells, i.e. both cell lines strongly require them. The cytotoxicity of 5 nM ADR was then examined in medium which included one or the other of them in stepwise levels varied at 80, 60, 40, 20 and 0% of the ordinary level. Change of Asn level caused a difference in ADR toxicity; also, the change of Gln level, especially the 60% level caused ADR toxicity of 5 nM, which is less than the IC50 value, in the proliferation of both cells. This suggested the usefulness of glutamine level modification on the enhancement of ADR cytotoxicity.

摘要

在含有10%胎牛血清和其他成分的培养基(RPMI 1640)中,单一氨基酸天冬酰胺(Asn)、谷氨酰胺(Gln)或脯氨酸缺失对阿霉素(ADR)细胞毒性的影响,在3天时间内对P388小鼠白血病细胞和CEM人急性淋巴细胞白血病细胞的生长进行了评估。在氨基酸缺失条件下的IC50值测定中,未观察到ADR细胞毒性增强。在无ADR培养基中单独缺失Gln或Asn明显抑制了两种细胞的增殖,即两种细胞系都强烈需要它们。然后在培养基中检测5 nM ADR的细胞毒性,该培养基中逐步改变Gln或Asn的含量,分别为正常水平的80%、60%、40%、20%和0%。Asn水平变化导致ADR毒性存在差异;同样,Gln水平变化,尤其是60%水平,导致5 nM ADR在两种细胞增殖中的毒性低于IC50值。这表明改变谷氨酰胺水平对增强ADR细胞毒性有用。

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Cancer Biochem Biophys. 1994 Sep;14(2):99-105.
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