Oxymatrine reverses 5-fluorouracil resistance by inhibition of colon cancer cell epithelial-mesenchymal transition and NF-κB signaling
| Autor: | Zheng Wen Cai, Jie Luo, Jun Wu, Jie An Huang, Ting‑Qing Gan, Zu Xuan Chen, Cheng Long Han, Li Wang, Li Liang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Oncogene Colorectal cancer Cell Articles Cell cycle Cell morphology medicine.disease 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oxymatrine Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research medicine Epithelial–mesenchymal transition |
| Zdroj: | Oncology letters. 19(1) |
| ISSN: | 1792-1074 |
| Popis: | The present study investigated the sensitization of 5-fluorouracil (5-FU)-resistant colon cancer cells in vitro, using oxymatrine, a Chinese herb, and a quinolizidine alkaloid compound extracted from the root of Sophora flavescens. The HCT-8 colon cancer cell line and its 5-FU-resistant subline HCT-8/5-FU were treated with 5-FU and oxymatrine, alone or in combination, at various doses. The cells were subsequently assessed for changes in cell viability, apoptosis and morphology and analyzed by fluorescence microscopy and western blotting. The data demonstrated that HCT-8/5-FU markedly increased the dose of 5-FU required for the suppression of tumor cell viability (78.77±1.90 µg/ml vs. 9.20±0.96 µg/ml in parental HCT-8 cells), whereas HCT-8/5-FU induced the tumor cell epithelial-mesenchymal transition (EMT). By contrast, oxymatrine alone and in combination with 5-FU altered HCT-8/5-FU cell morphology, apoptosis and EMT phenotypes. The combination of oxymatrine and 5-FU reduced the protein expression of snail family transcriptional repressor 2 and vimentin, phosphorylated p65 and induced the expression of E-cadherin, by inhibiting the nuclear factor κB (NF-κB) signaling pathway. In conclusion, the data from the present study demonstrated that EMT was associated with 5-FU chemoresistance in HCT-8/5-FU colon cancer cells, and that oxymatrine treatment was able to reverse such resistance. Oxymatrine may regulate tumor cell EMT and inactivate the NF-κB signaling pathway, and may therefore serve as a potential therapeutic drug to reverse 5-FU resistance in colon cancer cells. |
| Databáze: | OpenAIRE |
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