Generation of multidrug resistant lymphoma cell lines stably expressing P-glycoprotein.
Generation of multidrug resistant lymphoma cell lines stably expressing P-glycoprotein.
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DOI：
10.3892/or.19.4.889
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发表时间：
2008-04
期刊：
影响因子：
4.2
通讯作者：
Iliodora V. Pop;Laurentiu M. Pop;E. Vitetta;M. Ghetie
中科院分区：
文献类型：
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作者：
Iliodora V. Pop;Laurentiu M. Pop;E. Vitetta;M. Ghetie
本研究的目的是通过药物筛选获得表达P-糖蛋白(P-gp)的多药耐药(MDR)细胞系。由于我们之前的研究是在感染了P-gp载体的细胞上进行的，因此在药物选择产生的细胞中证实我们的发现是很重要的。在这篇报告中，我们描述了三个通过逐步暴露于长春新碱(VCR)而产生耐药性的B淋巴瘤细胞系：对18 NM VCR耐药的Raji细胞(R18V)，对21 NM VCR耐药的Namalwa细胞(N21V)和对12 NM VCR耐药的DHL-4细胞(DHL-4/12V)。细胞高表达P-gp，持续表达CD19、CD20和CD22，均为单抗治疗的靶点。根据罗丹明123和DIOC2的外流，这些新细胞中的P-gp泵是有功能的，这三个细胞系对几种化疗药物都有耐药性。我们进一步确定它们的P-gp表型在异种移植的SCID小鼠中是稳定的，并且肿瘤对化疗也是耐药的。我们现在将使用这些新的MDR细胞来确定抗CD19和-20的单抗是否可以逆转P-gp，正如我们之前使用感染了含有人类MDR1基因的逆转录病毒的Namalwa细胞所展示的那样。
The objective of this study was to generate new P-glycoprotein (P-gp)-expressing multidrug resistant (MDR) cell lines by drug selection. Since our previous studies have been carried out with cells infected with a P-gp-containing vector, it was important to confirm our findings in cells generated by drug selection. In this report, we describe three B-lymphoma cell lines which became drug-resistant by stepwise exposure to vincristine (VCR): Raji cells resistant to 18 nM VCR (R18V), Namalwa cells resistant to 21 nM VCR (N21V) and DHL-4 cells resistant to 12 nM VCR (DHL-4/12V). Cells overexpressed P-gp and continued to express CD19, CD20 and CD22, all of which are targets for monoclonal antibody (MAb) therapy. The P-gp pump in these new cells was functional as determined by the efflux of Rhodamine 123 and DIOC2, and the three cell lines were resistant to several chemotherapeutic drugs. We further determined that their P-gp phenotype was stable in xenografted SCID mice and that the tumors were also resistant to chemotherapy. We will now use these new MDR cells to determine whether monoclonal antibodies against CD19 and -20 can reverse P-gp, as we previously demonstrated using Namalwa cells infected with a human mdr1 gene-containing retrovirus.