Leukemia is a common malignancy affecting humans worldwide. Pirarubicin (Pira) is one of the anticancer agents used for the treatment of leukemia. Although Pira is effective, drug resistance may develop in cancer cells exposed to this drug, whereas the combination of natural products with Pira may help to overcome this problem. The aim of the present study was to focus on the effect of gallic acid (GA) on the anticancer activity of Pira in K562 leukemia cells and K562/doxorubicin (Dox)‑resistant leukemia cells in order to investigate the possible underlying mechanisms. The cell viability, mitochondrial activity, mitochondrial membrane potential (ΔΨm) and ATP levels were assessed in living K562 and K562/Dox cancer cells following treatment with GA/Pira combination, GA alone or Pira alone. P‑glycoprotein‑mediated efflux of Pira was determined in GA‑treated K562/Dox cancer cells. The results demonstrated that GA/Pira combination decreased cell viability, mitochondrial activity, ΔΨm and ATP levels in K562 and K562/Dox cancer cells in a GA concentration‑dependent manner compared with non‑treated or Pira‑treated cells. GA inhibited P‑glycoprotein‑mediated efflux of Pira in GA‑treated K562/Dox cancer cells. Therefore, GA enhanced the anticancer effect of Pira on K562 and K562/Dox cancer cells through cellular energy status impairment, and was able to reverse drug resistance in living K562/Dox cancer cells by inhibiting the function of P‑glycoprotein.

中文翻译：

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没食子酸通过细胞能量状态损伤和 P-糖蛋白抑制增强活体 K562 和 K562/Dox 白血病癌细胞中吡柔比星诱导的抗癌作用。

白血病是一种影响全世界人类的常见恶性肿瘤。吡柔比星（Pira）是一种用于治疗白血病的抗癌剂。尽管 Pira 有效，但暴露于该药物的癌细胞可能会产生耐药性，而天然产物与 Pira 的组合可能有助于克服这个问题。本研究的目的是关注没食子酸 (GA) 对 Pira 在 K562 白血病细胞和 K562/多柔比星 (Dox) 耐药性白血病细胞中的抗癌活性的影响，以研究可能的潜在机制。在用 GA/Pira 组合、单独的 GA 或单独的 Pira 处理后，在活的 K562 和 K562/Dox 癌细胞中评估细胞活力、线粒体活性、线粒体膜电位 (ΔΨm) 和 ATP 水平。在 GA 处理的 K562/Dox 癌细胞中测定了 P-糖蛋白介导的 Pira 外排。结果表明，与未处理或 Pira 处理的细胞相比，GA/Pira 组合以 GA 浓度依赖性方式降低了 K562 和 K562/Dox 癌细胞的细胞活力、线粒体活性、ΔΨm 和 ATP 水平。在 GA 处理的 K562/Dox 癌细胞中，GA 抑制了 P-糖蛋白介导的 Pira 外流。因此，GA通过细胞能量状态损伤增强了Pira对K562和K562/Dox癌细胞的抗癌作用，并能够通过抑制P-糖蛋白的功能逆转活K562/Dox癌细胞的耐药性。与未处理或 Pira 处理的细胞相比，K562 和 K562/Dox 癌细胞中的 ΔΨm 和 ATP 水平呈 GA 浓度依赖性。在 GA 处理的 K562/Dox 癌细胞中，GA 抑制了 P-糖蛋白介导的 Pira 外流。因此，GA通过细胞能量状态损伤增强了Pira对K562和K562/Dox癌细胞的抗癌作用，并能够通过抑制P-糖蛋白的功能逆转活K562/Dox癌细胞的耐药性。与未处理或 Pira 处理的细胞相比，K562 和 K562/Dox 癌细胞中的 ΔΨm 和 ATP 水平呈 GA 浓度依赖性。在 GA 处理的 K562/Dox 癌细胞中，GA 抑制了 P-糖蛋白介导的 Pira 外流。因此，GA通过细胞能量状态损伤增强了Pira对K562和K562/Dox癌细胞的抗癌作用，并能够通过抑制P-糖蛋白的功能逆转活K562/Dox癌细胞的耐药性。