Targeting CD133 reverses drug-resistance via the AKT/NF-κB/MDR1 pathway in colorectal cancer
| Autor: | Ke Xu, Ziyuan Wang, Zeting Yuan, Yanyan Qiu, Van Minh Le, Jian Xu, Jie Wang, Yueping Zhan, Wei Li, Jianhua Xu, Peihao Yin, Hai-Trieu Ly, Yijun Cao, Xin Liang |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
ATP Binding Cassette Transporter Subfamily B Molecular biology Colorectal cancer Apoptosis Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Cell Line Tumor medicine Humans AC133 Antigen neoplasms Protein kinase B Cell Proliferation 030304 developmental biology 0303 health sciences Cancer stem cells Chemistry NF-kappa B Transcription Factor RelA NF-κB medicine.disease Hedgehog signaling pathway Gene Expression Regulation Neoplastic Multiple drug resistance Oncology Doxorubicin Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell Cancer research Colorectal Neoplasms Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/s41416-020-0783-0 |
| Popis: | Background Recent studies have shown that multidrug resistance may be induced by the high stemness of cancer cells. Following prolonged chemotherapy, MDR protein 1 (MDR1) and CD133 increase in CRC, but the relationship between them is unclear. Methods The relationship between MDR and CSC properties in CRC was determined via CCK-8 assay, apoptosis assay, DOX uptake and retention, immunohistochemistry, immunofluorescence and flow cytometry. The correlations between their expression levels were evaluated using Spearman’s rank statistical test and the Mann-Whitney test. Furthermore, the effect of CD133 on the repression of the AKT/NF-κB/MDR1 signalling pathway was investigated in vitro and in vivo. Results We found that CD133 increased with the emergence of drug-resistance phenotypes, and the high expression of MDR1/P-gp was consistently accompanied by positive expression of CD133 as demonstrated by the analysis of patient samples. Up- or downregulation of CD133 could regulate MDR via AKT/NF-κB/MDR1 signalling in CRC. A rescue experiment showed that the AKT/NF-κB signalling pathway is the main mechanism by which CD133 regulates MDR1/P-gp expression in CRC. Conclusions Taken together, our results suggest that targeting CD133 reverses drug resistance via the AKT/NF-κB/MDR1 pathway and that this pathway might serve as a potential therapeutic target to reverse MDR in CRC. |
| Databáze: | OpenAIRE |
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