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首页> 外文期刊>Biology Open >Intercellular transfer of P-glycoprotein mediates the formation of stable multi-drug resistance in human bladder cancer BIU-87 cells
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Intercellular transfer of P-glycoprotein mediates the formation of stable multi-drug resistance in human bladder cancer BIU-87 cells

机译：P糖蛋白的细胞间转移介导人膀胱癌BIU-87细胞稳定的多药耐药性形成

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摘要

We investigated the biological characteristics of acquired drug-resistant cells (AqMDRs) formed by intercellular P-glycoprotein (P-gp) transfer and whether AqMDRs can form stable drug-resistant strains. Drug-sensitive BIU-87 cells were co-cultured with doxorubicin (DOX)-resistant derivative BIU-87/DOX cells in transwell chambers for up to 96?h. The presence of P-gp in recipient cell membranes (AqMDRs) was detected by confocal microscopy, CCK-8, western blot, and RT-PCR were used to detect resistance index (RI), P-gp expression andMDR1mRNA expression in AqMDRs after 0, 4, 8, 16, and 20 passages and frozen/resuscitated twentieth generation AqMDRs. There was an increase in P-gp transfer with longer co-culture times of drug-resistant and sensitive strains. Without DOX, although the AqMDR numbers increased with each passage, the RI and P-gp expression decreased gradually, and the expression level of MDR1 mRNA did not change significantly. With DOX, the RI and P-gp expression increased slightly, and the MDR1 mRNA expression level gradually increased to the BIU-87/DOX level. AqMDRs can grow stably at drug concentrations slightly higher than the IC50 of sensitive strains, which sensitive strains cannot survive. P-gp transfer between cells gradually increases with longer co-culturing of drug-resistant and sensitive strains. The drug resistance of AqMDRs decreases without drug intervention, but with drug intervention, cells can maintain resistance and gradually develop into stable drug-resistant cells.This article has an associated First Person interview with the first author of the paper.
机译：我们调查了由细胞间P-糖蛋白（P-gp）转移形成的获得性耐药细胞（AqMDRs）的生物学特性，以及AqMDRs是否可以形成稳定的耐药菌株。将对药物敏感的BIU-87细胞与抗阿霉素（DOX）的衍生物BIU-87 / DOX细胞在透孔腔中共培养长达96？h。共聚焦显微镜检测受体细胞膜（AqMDRs）中P-gp的存在，CCK-8，蛋白质印迹法和RT-PCR用于检测0后AqMDRs的抗性指数（RI），P-gp表达和MDR1mRNA表达。 ，第4、8、16和20代以及第20代冻结/复苏的AqMDR。随着耐药菌和敏感菌共培养时间的延长，P-gp的转移增加。没有DOX的情况下，尽管AqMDR的数目随着每次传代而增加，但RI和P-gp的表达逐渐降低，并且MDR1 mRNA的表达水平没有明显变化。使用DOX时，RI和P-gp表达略有增加，并且MDR1 mRNA表达水平逐渐增加至BIU-87 / DOX水平。 AqMDR可以在药物浓度略高于敏感菌株的IC50的情况下稳定生长，而敏感菌株无法生存。随着耐药菌株和敏感菌株的共同培养时间的延长，细胞之间的P-gp转移逐渐增加。在没有药物干预的情况下，AqMDRs的耐药性会降低，但是在药物干预下，细胞可以维持耐药性并逐渐发展成稳定的耐药细胞。本文与第一作者相关的第一人称采访。

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