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. 2023 Oct;50(10):8551-8563.
doi: 10.1007/s11033-023-08737-2. Epub 2023 Aug 29.

Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines

Ayse Banu Demir  1 , Elif Baris  2 , Umay Bengi Kaner  3 , Hani Alotaibi  4   5 , Nese Atabey  5   6 , Ahmet Koc  7
Affiliations

Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines

Ayse Banu Demir et al. Mol Biol Rep. 2023 Oct.

Abstract

Background: 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.

Methods and results: 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.

Conclusions: 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.

Keywords: Cancer drug resistance; Doxorubicin; Hepatocellular carcinoma; Toll-interacting protein.

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References

    1. Rumgay H, Arnold M, Ferlay J et al (2022) Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 77:1598–1606. https://doi.org/10.1016/j.jhep.2022.08.021 - DOI - PubMed
    1. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660 - DOI - PubMed
    1. Wong MCS, Jiang JY, Goggins WB et al (2017) International incidence and mortality trends of liver cancer: a global profile. Sci Rep 7:45846. https://doi.org/10.1038/srep45846 - DOI - PubMed
    1. Thomas MB, Zhu AX (2005) Hepatocellular Carcinoma: the need for Progress. J Clin Oncol 23:2892–2899. https://doi.org/10.1200/JCO.2005.03.196 - DOI - PubMed
    1. Tian T, Fu X, Lu J et al (2018) MicroRNA-760 inhibits Doxorubicin Resistance in Hepatocellular Carcinoma through regulating Notch1/Hes1-PTEN/Akt signaling pathway. J Biochem Mol Toxicol 32:e22167. https://doi.org/10.1002/jbt.22167 - DOI - PubMed

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