薄荷醇具有放松、抗菌和抗炎活性，并作为功能性食品和治疗药物上市。本研究使用HepG2细胞，考察薄荷醇对多药耐药相关蛋白2 (MRP2)表达的影响以及其与表阿霉素（EPI）和顺铂（CIS）细胞毒性的关联。通过实时聚合酶链反应检测目标基因的表达水平。通过高效液相色谱测定细胞内EPI的浓度。通过MTT分析评估细胞存活率。薄荷醇作用24小时后，MRP2 mRNA的表达显著增加。与先前的报告一致，MRP2的增加表达与Akt功能抑制呈负相关。HepG2细胞暴露于薄荷醇后，EPI的细胞内积累显著减少，并且薄荷醇暴露的HepG2细胞中剩余EPI的细胞内浓度也显著降低。通过MK-571处理，而非维拉帕米处理，显著抑制了EPI细胞内积累的减少。EPI和CIS均对HepG2细胞产生细胞毒性效应，但是薄荷醇预处理24小时后，细胞存活率的下降显著减弱。这些结果表明，薄荷醇通过MRP2的诱导，使肝细胞癌对EPI和CIS等抗癌药物产生耐药性。 版权声明：© 2023 Nagai等。本文在「保持署名权」的知识共享许可协议下进行发表，允许在任何媒介中自由使用、分发和传播本文，只要原作者和来源被明确地署名。

Menthol exerts relaxing, antibacterial, and anti-inflammatory activities, and is marketed as a functional food and therapeutic drug.In the present study, the effects of menthol on the expression of multidrug resistance associated protein 2 (MRP2) and its association with the cytotoxicity of epirubicin (EPI) and cisplatin (CIS) were examined using HepG2 cells.The expression levels of target genes were examined by real-time PCR. The intracellular concentration of incorporated EPI was measured by high-performance liquid chromatography. Cell viability was evaluated by MTT analysis.The expression of MRP2 mRNA was increased by exposing HepG2 cells to menthol for 24 hr. Consistent with a previous report suggesting an inverse correlation between MRP2 and Akt behavior, increased expression of MRP2 was also observed on suppression of the Akt function. Intracellular accumulation of EPI was significantly decreased by exposure of HepG2 cells to menthol, and a significant decrease in the intracellular concentration of EPI remaining was observed in HepG2 cells exposed to menthol. The decreased intracellular accumulation of EPI was significantly suppressed by treatment with MK-571, but not verapamil. Both EPI and CIS exerted cytocidal effects on HepG2 cells, but the decrease in cell viability was significantly attenuated by 24-hr menthol pre-exposure.These results demonstrate that menthol causes hepatocellular carcinoma to acquire resistance to anticancer drugs such as EPI and CIS by MRP2 induction.Copyright: © 2023 Nagai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.