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首页> 外文期刊>Mutation Research, C. Mutation Research Letters >CHARACTERIZATION OF CARBOPLATIN-RESISTANT SUBLINES DERIVED FROM HUMAN LARYNX CARCINOMA CELLS
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CHARACTERIZATION OF CARBOPLATIN-RESISTANT SUBLINES DERIVED FROM HUMAN LARYNX CARCINOMA CELLS

机译：源自人喉癌细胞的抗碳素亚基的表征

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In human larynx carcinoma cells, resistance to carboplatin (CBDCA) was induced by continuous five-day exposure of parental lines to the increasing CBDCA concentrations in culture medium, reaching the clinical level of 9.23 mu g/ml. Three clones were selected and characterized: CBP-3, CBP-6 and CBP-7. CBP-3 clone was 2.0-fold, CBP-6 2.1-fold, and CBP-7 2.9-fold more resistant to carboplatin. The response of these sublines to different cytostatics was compared to the response of the parental cell lines to the same drug. CBP-7 and CBP-6 clones exhibited cross-resistance to cisplatin (cis-DDP), CBP-7 clone became markedly more sensitive and CBP-3 slightly more sensitive to 5-fluorouracil (5-FU), CBP-6 became sensitive to etoposide (Et), CBP-6 became sensitive and CBP-7 resistant to vinblastine (VBL). Other clones did not change change their sensitivity to cls-DDP, 5-FU, Et or VBL. None of the three clones did alter the sensitivity to mitomycin C, doxorubicin (Dox) or vincristine (VCR). There was no change in the growth rate. Glutathione (GHS) levels were elevated in all three clones, but the increase was significant only for CBP-7 clone. Similarly, the activity of glutathione transferase (GST) was elevated in all clones, but this increase was not significant for CBP-7 clone. The analysis of the of c-myc, c-Ha-ras and c-fos genes reveal no change in the c-myc expression, induction of the c-Ha-ras oncogene in CBP-6 and CBP-7 cells, and increased expression of the c-fos in CBP-6 and CPB-7 clones. The cross-resistance profiles, GSH and GST biochemistry and oncogene expression indicate that the acquired resistance to carboplatin is a complex, multifactorial process in these cells.
机译：在人类喉癌细胞中，通过将亲本系连续五天暴露于培养基中不断增加的CBDCA浓度来诱导对卡铂（CBDCA）的耐药性，达到临床水平9.23μg / ml。选择并鉴定了三个克隆：CBP-3，CBP-6和CBP-7。 CBP-3克隆对卡铂的耐药性是后者的2.0倍，CBP-6的2.1倍和CBP-7的2.9倍。将这些亚系对不同细胞抑制剂的反应与亲本细胞系对相同药物的反应进行了比较。 CBP-7和CBP-6克隆对顺铂（cis-DDP）表现出交叉耐药性，CBP-7克隆对5-氟尿嘧啶（5-FU）更加敏感，而CBP-3对5-氟尿嘧啶（5-FU）更加敏感，CBP-6对于依托泊苷（Et），CBP-6变得敏感，而CBP-7对长春碱（VBL）产生抗性。其他克隆没有改变，改变了它们对cls-DDP，5-FU，Et或VBL的敏感性。这三个克隆均未改变对丝裂霉素C，阿霉素（Dox）或长春新碱（VCR）的敏感性。增长率没有变化。谷胱甘肽（GHS）水平在所有三个克隆中均升高，但该升高仅对CBP-7克隆显着。同样，在所有克隆中谷胱甘肽转移酶（GST）的活性均升高，但这种升高对于CBP-7克隆并不明显。对c-myc，c-Ha-ras和c-fos基因的分析表明，c-myc表达没有变化，在CBP-6和CBP-7细胞中诱导了c-Ha-ras癌基因，并且增加了c-fos在CBP-6和CPB-7克隆中的表达。交叉耐药谱，GSH和GST生物化学以及癌基因表达表明，获得的对卡铂的耐药性是这些细胞中复杂，多因素的过程。

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