Article ; Online: Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.
2023 Volume 50, Issue 10, Page(s) 8551–8563
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 ... ...
| 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. |
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| MeSH term(s) | Humans ; Apoptosis ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Saccharomyces cerevisiae ; Intracellular Signaling Peptides and Proteins/genetics |
| Chemical Substances | Doxorubicin (80168379AG) ; TOLLIP protein, human ; Intracellular Signaling Peptides and Proteins |
| Language | English |
| Publishing date | 2023-08-29 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 186544-4 |
| ISSN | 1573-4978 ; 0301-4851 |
| ISSN (online) | 1573-4978 |
| ISSN | 0301-4851 |
| DOI | 10.1007/s11033-023-08737-2 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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