阿霉素诱导蛋白与耐药免疫母细胞B淋巴瘤的药物敏感性相关

Chuck C.-K. Chao , Wai-Ching Yam , Kuo-Chen Chung , Yat-Sen Ho
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引用次数: 1

摘要

我们之前已经建立了一个免疫母细胞B淋巴瘤细胞系,命名为HOB1。这种细胞系对多种化疗药物都非常敏感。在阿霉素和其他药物的IC50(抑制细胞生长50%的浓度)作用下,两个64 kDa左右的共调节多肽(称为p64)被诱导10 - 30倍。这些诱导蛋白以单体形式定位于细胞质部分,等电点pH = 6.2(主要蛋白)和pH = 7.0(次要蛋白)。利用HOB1细胞建立了阿霉素耐药细胞系。在对阿霉素毒性表现出表型抗性的HOB1细胞或不相关的细胞系中,p64的诱导性显著降低。耐药细胞中p64诱导性的丧失不是由于细胞吸收阿霉素的失败,因为药物积累动力学与亲本细胞保持相同。
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Adriamycin-inducible proteins associated with drug sensitivity in resistant immunoblastic B lymphoma cells

We have previously established an immunoblastic B lymphoma cell line, designated HOB1. This cell line is hypersensitive to a wide spectrum of chemotherapeutic agents. Two co-regulated polypeptides around 64 kDa (termed p64) were induced 10–30-fold in response to adriamycin and some other drugs at the IC50 (the concentration inhibiting cell growth by 50%). These inducible proteins are localized as monomeric forms in the cytosolic fraction, with isoelectric points of pH = 6.2 (major protein) and pH = 7.0 (minor protein). An adriamycin-resistant cell line was established from HOB1 cells. The p64 inducibility was dramatically reduced in resistant HOB1 cells or unrelated cell lines which show phenotypic resistant to adriamycin toxicity. The loss of p64 inducibility in resistance cells is not due to a failure of cells to take up adriamycin since drug accumulation kinetics remained the same as in the parental cells.

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