<p>Leukemia is a hematologic malignancy commonly treated with chemotherapy. However, P-glycoprotein (P-gp)–mediated drug resistance remains a major barrier to effective treatment. To investigate the effects of pre-irradiated with low-dose radiation (LDR) followed by 4-hydroxybenzoic acid (4-HBA) and vanillic acid (VA) treatments on P-gp-mediated efflux pirarubicin (Pira) in living multidrug-resistant K562/Dox cells. Cells were exposed to X-rays at total radiation doses of 0, 0.02, 0.05, and 0.1&#xa0;Gy. At 24&#xa0;h following irradiation, 4-HBA and VA (5 and 10&#xa0;mM) were added to the irradiated cells. The cell viability was assessed at 48&#xa0;h after irradiation, and succinate dehydrogenase (SDH) activity, mitochondrial membrane potential (ΔΨm), and adenosine triphosphate (ATP) levels were examined at 28&#xa0;h after irradiation. In addition, the functioning of P-gp-mediated efflux Pira was investigated in living multidrug-resistant K562/Dox cells at 28&#xa0;h after irradiation. Pre-exposure to LDR followed by 4-HBA and VA treatment significantly decreased cell viability in K562 cells and K562/dox cells when compared to the control. Similarly, pre-exposure to LDR followed by 4-HBA and VA treatment in K562 and K562/Dox cells significantly decreased SDH activity. Additionally, |ΔΨm| and % ATP values had changed when compared to the control. Furthermore, pre-exposure to LDR following treatment with 4-HBA and VA in K562/Dox cells increased the inhibition functioning of P-gp. 4-HBA and VA non-competitively inhibited the P-gp-mediated efflux of Pira. Pre-exposure to LDR followed by 4-HBA and VA treatment could provoke the impairment of energetic state in K562 and K562/Dox cells and also decreases P-gp function in K562/Dox cells.</p>

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The effects of low-dose X-ray pre-irradiation followed by 4-hydroxybenzoic acid and vanillic acid on P-glycoprotein-mediated efflux pirarubicin in multidrug-resistant K562/Dox cells

  • Ohnmar Myint,
  • Benjamaporn Supawat,
  • Suchart Kothan,
  • Montree Tungjai

摘要

Leukemia is a hematologic malignancy commonly treated with chemotherapy. However, P-glycoprotein (P-gp)–mediated drug resistance remains a major barrier to effective treatment. To investigate the effects of pre-irradiated with low-dose radiation (LDR) followed by 4-hydroxybenzoic acid (4-HBA) and vanillic acid (VA) treatments on P-gp-mediated efflux pirarubicin (Pira) in living multidrug-resistant K562/Dox cells. Cells were exposed to X-rays at total radiation doses of 0, 0.02, 0.05, and 0.1 Gy. At 24 h following irradiation, 4-HBA and VA (5 and 10 mM) were added to the irradiated cells. The cell viability was assessed at 48 h after irradiation, and succinate dehydrogenase (SDH) activity, mitochondrial membrane potential (ΔΨm), and adenosine triphosphate (ATP) levels were examined at 28 h after irradiation. In addition, the functioning of P-gp-mediated efflux Pira was investigated in living multidrug-resistant K562/Dox cells at 28 h after irradiation. Pre-exposure to LDR followed by 4-HBA and VA treatment significantly decreased cell viability in K562 cells and K562/dox cells when compared to the control. Similarly, pre-exposure to LDR followed by 4-HBA and VA treatment in K562 and K562/Dox cells significantly decreased SDH activity. Additionally, |ΔΨm| and % ATP values had changed when compared to the control. Furthermore, pre-exposure to LDR following treatment with 4-HBA and VA in K562/Dox cells increased the inhibition functioning of P-gp. 4-HBA and VA non-competitively inhibited the P-gp-mediated efflux of Pira. Pre-exposure to LDR followed by 4-HBA and VA treatment could provoke the impairment of energetic state in K562 and K562/Dox cells and also decreases P-gp function in K562/Dox cells.