Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
Molecular biology reports - 50(2023), 10 vom: 29. Aug., Seite 8551-8563 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Demir, Ayse Banu [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Cancer drug resistance |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s11033-023-08737-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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SPR053190289 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Hepatocellular carcinoma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Toll-interacting protein |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a Cancer drug resistance |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Baris, Elif |0 (orcid)0000-0001-6838-7932 |4 aut | |
| 700 | 1 | |a Kaner, Umay Bengi |4 aut | |
| 700 | 1 | |a Alotaibi, Hani |0 (orcid)0000-0001-7423-9653 |4 aut | |
| 700 | 1 | |a Atabey, Nese |0 (orcid)0000-0003-4966-2980 |4 aut | |
| 700 | 1 | |a Koc, Ahmet |0 (orcid)0000-0003-3484-2137 |4 aut | |
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