肝癌是全球癌症相关死亡的第三大原因，肝细胞癌（HCC）是最常见的肝癌类型。在移植前几乎无法手术的区域以及电化学治疗中，经动脉介入是一种化疗方法。在电化学治疗中使用了柔红霉素，然而，治疗的效果受到抗药性机制的影响。之前我们发现，CUE5基因的过度表达导致酿酒酵母（S. cerevisiae）对柔红霉素具有抗药性。在本研究中，通过评估人类CUE5同源蛋白Toll-interacting protein（TOLLIP）对肝细胞癌细胞抗柔红霉素性的影响，旨在确定其在增加经动脉介入疗法的有效性中的可能作用。使用NIH Gene Expression Omnibus（GEO）和Oncomine数据集分析了TOLLIP表达较低和较高的HCC细胞系，并选择了SNU449和Hep3B细胞系。通过质粒转染增加TOLLIP表达，并通过TOLLIP-siRNA减少TOLLIP表达，分别在两种细胞系中利用RT-PCR和ELISA评估其表达水平。在柔红霉素处理后使用xCELLigence和MTT实验检测细胞增殖和存活率，并评估生长抑制50（GI 50）浓度。沉默TOLLIP后，48小时药物处理后，两种细胞系的柔红霉素GI 50浓度减少了约2倍。我们的研究首次表明，在肝细胞癌细胞中沉默TOLLIP可能有助于使这些细胞对柔红霉素更加敏感，并增加了使用柔红霉素的化疗方案的有效性。© 2023. 作者（们），在Springer Nature B.V.独家许可下。

Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions.The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48 h of drug treatment.Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.