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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Modulatory effects of heparin on cellular accumulation and cytotoxicity of doxorubicin in MRP1-overexpressing HL60/doxo cells.
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Modulatory effects of heparin on cellular accumulation and cytotoxicity of doxorubicin in MRP1-overexpressing HL60/doxo cells.

机译：肝素对过表达MRP1的HL60 / doxo细胞中阿霉素的细胞蓄积和细胞毒性的调节作用。

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BACKGROUND: The overexpression of multidrug resistance protein (MRP1), associated with high levels of intracellular glutathione (GSH), is a well characterized mechanism of multidrug resistance (MDR) in several malignancies. Various chemosensitizers have been used in vitro to modulate the MRP1 activity, but the high toxicity limits their clinical application. Unfractionated heparin (UFH), is frequently used to prevent thrombo-embolic complications in cancer patients. This in vitro study aimed to elucidate the potential role of UFH as a sensitizer in anticancer clinical chemotherapy. MATERIALS AND METHODS: The human leukemic doxorubicin-resistant cell line (HL60/doxo), which overexpresses the MRP1 protein was treated with UFH alone or in combination with three different concentrations of doxo. The intracellular accumulation and cytotoxicity of doxo and the cellular GSH content were measured in comparison with the leukotriene LTD4 receptor antagonist, MK571, a specific MRP1 inhibitor. RESULTS: UFH increased doxo accumulation and cytotoxicity in the HL60/doxo cell line with respect to cells treated with doxo alone. UFH also decreased the cellular GSH content in the HL60/doxo cells with respect to the control, suggesting a potential involvement of UFH in doxo co-transport with GSH. CONCLUSION: Our results demonstrate that UFH modulates MRP1-mediated MDR in HL60/doxo cells expressing high MRP1 levels. These findings suggest a potential clinical application of heparin as an adjuvant to overcome MRP1-mediated drug resistance in cancer patients.
机译：背景：与高水平的细胞内谷胱甘肽（GSH）相关的多药耐药蛋白（MRP1）的过表达是几种恶性肿瘤中多药耐药（MDR）的机制。体外已经使用了各种化学增敏剂来调节MRP1活性，但是高毒性限制了它们的临床应用。普通肝素（UFH）通常用于预防癌症患者的血栓栓塞并发症。这项体外研究旨在阐明UFH在抗癌临床化学疗法中作为敏化剂的潜在作用。材料与方法：UFH单独或与三种不同浓度的doxo联合处理过表达MRP1蛋白的人白血病抗阿霉素细胞系（HL60 / doxo）。与白三烯LTD4受体拮抗剂MK571（一种特定的MRP1抑制剂）相比，测量了doxo的细胞内积累和细胞毒性以及细胞中GSH的含量。结果：相对于单独用doxo处理的细胞，UFH增加了HL60 / doxo细胞系中doxo的积累和细胞毒性。相对于对照，UFH还降低了HL60 / doxo细胞中的细胞GSH含量，表明UFH可能与GSH共转运doxo。结论：我们的结果表明，UFH调节表达高MRP1水平的HL60 / doxo细胞中MRP1介导的MDR。这些发现表明，肝素作为克服癌症患者中MRP1介导的耐药性的佐剂的潜在临床应用。

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