Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2
Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2
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DOI：
10.1158/1535-7163.mct-05-0182
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发表时间：
2005-12-01
影响因子：
5.7
通讯作者：
Fan, DM
中科院分区：
文献类型：
--
作者：
Hong, L;Piao, Y;Fan, DM
本研究旨在探讨锌带结构域1（ZNRD 1）在白血病细胞多药耐药（MDR）中的作用及其可能的机制。ZNRD 1在长春新碱诱导的多药耐药白血病细胞HL-60/vincristine中的表达高于其亲本细胞HL-60。ZNRD 1表达上调可使HL-60细胞对P-糖蛋白（P-gp）相关和非相关药物产生耐药性，并抑制阿霉素诱导的细胞凋亡，同时减少阿霉素的蓄积，增加阿霉素的释放量。ZNRD 1可显著上调白血病细胞P-gp、Bcl-2的表达及MDR 1基因的转录，但对MDR相关蛋白的表达、谷胱甘肽S-转移酶活性及细胞内谷胱甘肽含量无明显影响。此外，通过RNA干扰或P-gp抑制剂抑制ZNRD 1表达可部分逆转ZNRD 1介导的MDR。对ZNRD 1生物学功能的深入研究将有助于了解白血病多药耐药的机制，为白血病的治疗提供新的思路。
Here, we investigated the role of zinc ribbon domain-containing 1 (ZNRD1) in multidrug resistance (MDR) of leukemia cells and the possible underlying mechanisms. ZNRD1 was found overexpressed in the vincristine-induced MDR leukemia cell HL-60/vincristine moreso than its parental cell HL-60. Up-regulation of ZNRD1 expression could confer resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on HL-60 cells and suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased releasing amount of Adriamycin. ZNRD1 could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene but not alter the expression of MDR-associated protein, glutathione S-transferase activity, or intracellular glutathione content in leukemia cells. In addition, inhibition of ZNRD1 expression by RNA interference or P-gp inhibitor could partially reverse ZNRD1-mediated MDR. The further study of the biological functions of ZNRD1 may be helpful for understanding the mechanisms of MDR of leukemia and developing possible strategies to treat leukemia.