Synergistic Effect of Baicalin and Adriamycin in Resistant HL-60/ADM Leukaemia Cells
Synergistic Effect of Baicalin and Adriamycin in Resistant HL-60/ADM Leukaemia Cells
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DOI：
10.1159/000480420
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Hu, Jianda
中科院分区：
文献类型：
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作者：
Zheng, Jing;Asakawa, Tetsuya;Hu, Jianda
背景/目的：本研究旨在探讨多药耐药（MDR）相关基因的表达，验证黄芩苷和阿霉素（ADM）的协同作用，并探讨ADM耐药白血病HL-60/ADM细胞的相关机制。方法：我们使用 HL-60/ADM 细胞系。采用细胞毒性和流式细胞术测定来验证黄芩苷的细胞毒性作用。使用实时聚合酶链反应和蛋白质印迹分析来评估MDR相关基因的表达以及黄芩苷诱导的基因表达变化（MDR相关和PI3K/Akt途径相关）。结果：我们发现HL-60和HL-60/ADM细胞中仅表达多药耐药蛋白1（MRP1）、肺耐药相关蛋白（LRP）和Bcl-2基因。 HL-60/ADM 细胞表现出显着较高的表达 (p < 0.05)。我们还观察到低剂量黄芩苷(5和10μmol/L)可通过增加ADM在细胞内的积累而诱导HL-60/ADM细胞的生长抑制和凋亡作用。验证了黄芩苷与ADM的协同作用。关于该过程中涉及的潜在机制，我们发现黄芩苷下调了多个 MDR 相关和 PI3K/Akt 通路相关基因的表达。结论：我们证实，与常规 HL-60 细胞相比，HL-60/ADM 细胞中 MRP1、LRP 和 Bcl-2 基因的表达增加，建议用于未来的 MDR 研究。本研究提供了黄芩苷和 ADM 在 HL-60/ADM 细胞中协同作用的证据。因此，黄芩苷可被认为是抗耐药白血病的潜在治疗剂。抑制 PI3K/Akt 信号通路，进而抑制 MDR 相关基因的表达可能是与 ADM 联合治疗降低 ADM 耐药性的常见机制。 (C) 2017 作者由 S. Karger AG 出版，巴塞尔
Background/Aims: The present study was designed to investigate the expression of multidrug resistance (MDR)-related genes, verify the synergistic effects of baicalin and Adriamycin (ADM) and investigate the related mechanisms in ADM-resistant leukaemic HL-60/ADM cells. Methods: We used a HL-60/ADM cell line. Cytotoxicity and flow cytometry assays were employed to verify the cytotoxic effects of baicalin. Real-time polymerase chain reaction and Western blotting assays were used to assess the expression of MDR-related genes and the changes in gene expression (both MDR-related and PI3K/Akt pathway-related) induced by administration of baicalin. Results: We found that only multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and Bcl-2 genes were expressed in both HL-60 and HL-60/ADM cells. HL-60/ADM cells exhibited significantly higher expression (p < 0.05). We also observed that low-dose baicalin (5 and 10 mu mol/L) can induce growth inhibition and apoptotic effects on HL-60/ADM cells by increasing the intracellular accumulation of ADM. The synergistic effect of baicalin and ADM was verified. Concerning the potential mechanisms involved in this process, we showed that baicalin down-regulated the expression of several MDR-related and PI3K/Akt pathway-related genes. Conclusions: We confirmed the increased expression of MRP1, LRP and Bcl-2 genes in HL-60/ADM cells compared to regular HL-60 cells, which are recommended for future investigation on MDR. The present study provided evidence of the synergistic effect of baicalin and ADM in HL-60/ADM cells. Therefore, baicalin may be considered as a potential therapeutic agent against resistant leukaemia. Suppression of the PI3K/Akt signalling pathway, followed by inhibition of the expression of MDR-related genes may be a common mechanism in combination treatments with ADM for the reduction of resistance to ADM. (C) 2017 The Author(s) Published by S. Karger AG, Basel