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首页> 外文期刊>Life sciences >Reversal of P-glycoprotein expressed in Escherichia coli leaky mutant by ascorbic acid.
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Reversal of P-glycoprotein expressed in Escherichia coli leaky mutant by ascorbic acid.

机译：抗坏血酸逆转大肠杆菌漏失突变体中表达的P-糖蛋白。

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It has been reported that functional expression of the multidrug resistance protein P-glycoprotein (P-gp) in E. coli is useful for screening P-gp substrates and inhibitors. In the present study, we have constructed by nitrosoguanidine and UV mutagenesis 28 leaky mutants of E. coli UT5600. These mutants are significantly susceptible to the toxic effect of known P-gp substrates and lipophilic cancer drugs. Mouse mdr1 was functionally expressed in the most permeable E. coli mutant (UTP17). Expression of P-gp in this mutant confers cross-resistance to mitomycin C, tegafur, daunorubicin, rhodamine 6G, tetraphenylphosphonium bromide and ciprofloxacin. To examine the reversal of P-gp expressed in this heterologous system, UTP17 cells expressing mouse mdr1 or lac permease as negative control were treated with various concentrations of mitomycin C with or without ascorbic acid. We found that ascorbic acid abrogated P-gp mediated multidrug resistance, suggesting that ascorbic acid might be used in combination with anticancer drugs to reduce emergence of multidrug resistance. We also demonstrated that tomato lectin antagonized the inhibitory action of ascorbic acid. This study provide a heterologous system for mdr1 expression in E. coli leaky mutant that can be used as a system for the screening of P-gp inducers and inhibitors, since it is quick and simple.
机译：据报道，在大肠杆菌中多药抗性蛋白P-糖蛋白（P-gp）的功能表达可用于筛选P-gp底物和抑制剂。在本研究中，我们已经通过亚硝基胍和紫外线诱变构建了28株大肠杆菌UT5600渗漏突变体。这些突变体对已知的P-gp底物和亲脂性癌症药物的毒性作用非常敏感。小鼠mdr1在功能最强的大肠杆菌突变体（UTP17）中表达。 P-gp在此突变体中的表达赋予丝裂霉素C，替加福，柔红霉素，若丹明6G，溴化四苯基phosph和环丙沙星交叉耐药性。为了检查在此异源系统中表达的P-gp的逆转，将表达小鼠mdr1或lac通透酶作为阴性对照的UTP17细胞用各种浓度的丝裂霉素C或不加抗坏血酸处理。我们发现抗坏血酸消除了P-gp介导的多药耐药性，这表明抗坏血酸可与抗癌药物联合使用以减少多药耐药性的出现。我们还证明了番茄凝集素拮抗抗坏血酸的抑制作用。这项研究提供了一种在大肠杆菌渗漏突变体中表达mdr1的异源系统，该系统可快速简便地用作筛选P-gp诱导剂和抑制剂的系统。

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