Donafenib activates the p53 signaling pathway in hepatocellular carcinoma, induces ferroptosis, and enhances cell apoptosis
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| Publicado en: | Clinical and Experimental Medicine vol. 25, no. 1 (Dec 2025), p. 29 |
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| Autor principal: | |
| Otros Autores: | , , , , , , , , |
| Publicado: |
Springer Nature B.V.
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| Acceso en línea: | Citation/Abstract Full Text Full Text - PDF |
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MARC
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| 003 | UK-CbPIL | ||
| 022 | |a 1591-8890 | ||
| 022 | |a 1591-9528 | ||
| 024 | 7 | |a 10.1007/s10238-024-01550-6 |2 doi | |
| 035 | |a 3256339859 | ||
| 045 | 2 | |b d20251201 |b d20251231 | |
| 084 | |a 65728 |2 nlm | ||
| 100 | 1 | |a Liang, Jiaming |u the First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary Surgery, Nanning, China (GRID:grid.412594.f) | |
| 245 | 1 | |a Donafenib activates the p53 signaling pathway in hepatocellular carcinoma, induces ferroptosis, and enhances cell apoptosis | |
| 260 | |b Springer Nature B.V. |c Dec 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Donafenib is an improved version of sorafenib in which deuterium is substituted into the drug’s chemical structure, enhancing its stability and antitumor activity. Donafenib exhibits enhanced antitumor activity and better tolerance than sorafenib in preclinical and clinical studies. However, the specific mechanism of its effect on hepatocellular carcinoma has not been reported. Iron deposition is a cell death pattern caused by disturbances in iron metabolism. Apoptosis is a form of programmed cell death. They may interact with each other during cell death. This study mainly explores the potential mechanism of donafenib activating the p53 signaling pathway, inducing iron deposition, and enhancing cell apoptosis in hepatocellular carcinoma. Hepa1-6 and Huh7 cells were treated with various concentrations of donafenib. Scratch healing and pore migration tests were conducted. Analyze apoptosis through flow cytometry and TUNEL fluorescence labeling. RNA sequencing was conducted on both untreated and donafenib-treated Huh7 cells. The key proteins involved in ferroptosis (SLC7A11, GPX4) and apoptosis (caspase3, caspase8, Bax, Bcl-2, p53) were then evaluated using immunoblotting and immunohistochemical staining. Reactive oxygen species (ROS) levels in the cancer cells were measured. Donafenib treatment resulted in a dose-dependent decrease in the proliferation, migration, and invasion capabilities of cancer cells. There was an increase in apoptosis rates and ROS accumulation, and a reduction in tumor volume. The key proteins involved in ferroptosis and apoptosis underwent significant changes. Donafenib activates the p53 signaling pathway, induce ferroptosis, and enhance apoptosis, suggesting its potential as an effective therapeutic agent for HCC. | |
| 651 | 4 | |a China | |
| 653 | |a p53 Protein | ||
| 653 | |a Monoclonal antibodies | ||
| 653 | |a Ferroptosis | ||
| 653 | |a Cell death | ||
| 653 | |a Metastasis | ||
| 653 | |a Cancer therapies | ||
| 653 | |a Antitumor activity | ||
| 653 | |a Cell proliferation | ||
| 653 | |a BAX protein | ||
| 653 | |a Bcl-2 protein | ||
| 653 | |a Reactive oxygen species | ||
| 653 | |a Metabolism | ||
| 653 | |a Liver cancer | ||
| 653 | |a Flow cytometry | ||
| 653 | |a Apoptosis | ||
| 653 | |a Immunoblotting | ||
| 653 | |a Kinases | ||
| 653 | |a Drug resistance | ||
| 653 | |a Cell culture | ||
| 653 | |a Statistical analysis | ||
| 653 | |a Oxidative stress | ||
| 653 | |a Medical prognosis | ||
| 653 | |a Hepatocellular carcinoma | ||
| 653 | |a Iron | ||
| 653 | |a Polyclonal antibodies | ||
| 653 | |a Glutathione | ||
| 653 | |a Signal transduction | ||
| 700 | 1 | |a Chen, Meifeng |u the First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary Surgery, Nanning, China (GRID:grid.412594.f) | |
| 700 | 1 | |a Yan, Guohong |u the First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary Surgery, Nanning, China (GRID:grid.412594.f) | |
| 700 | 1 | |a Hoa, Pham Thi Thai |u Guangxi International Zhuang Medical Hospital, Research and Development Centre of Zhuang and Yao Medicines, Nanning, China (GRID:grid.412594.f) | |
| 700 | 1 | |a Wei, Shuxin |u Guangxi Medical University, School of Basic Medical Sciences, Nanning, China (GRID:grid.256607.0) (ISNI:0000 0004 1798 2653) | |
| 700 | 1 | |a Huang, Hailian |u Guangxi Medical University, School of Basic Medical Sciences, Nanning, China (GRID:grid.256607.0) (ISNI:0000 0004 1798 2653) | |
| 700 | 1 | |a Xie, Qichong |u Guangxi Medical University, School of Basic Medical Sciences, Nanning, China (GRID:grid.256607.0) (ISNI:0000 0004 1798 2653) | |
| 700 | 1 | |a Luo, Xiaoling |u Guangxi Medical University, School of Basic Medical Sciences, Nanning, China (GRID:grid.256607.0) (ISNI:0000 0004 1798 2653) | |
| 700 | 1 | |a Mo, Shutian |u the First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary Surgery, Nanning, China (GRID:grid.412594.f) | |
| 700 | 1 | |a Han, Chuangye |u the First Affiliated Hospital of Guangxi Medical University, Department of Hepatobiliary Surgery, Nanning, China (GRID:grid.412594.f) | |
| 773 | 0 | |t Clinical and Experimental Medicine |g vol. 25, no. 1 (Dec 2025), p. 29 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3256339859/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3256339859/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3256339859/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |