The Antitumor and Sorafenib-resistant Reversal Effects of Ursolic Acid on Hepatocellular Carcinoma via Targeting ING5.
| Autor: | Fan YJ; College of Integrated Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110001, Liaoning Province, China., Pan FZ; Department of Ultrasound Medicine, Liaoning Cancer Hospital, Shenyang 110001, Liaoning Province, China., Cui ZG; Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui 910-1193, Japan., Zheng HC; Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China.; Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China. |
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| Jazyk: | angličtina |
| Zdroj: | International journal of biological sciences [Int J Biol Sci] 2024 Aug 05; Vol. 20 (11), pp. 4190-4208. Date of Electronic Publication: 2024 Aug 05 (Print Publication: 2024). |
| DOI: | 10.7150/ijbs.97720 |
| Abstrakt: | Inhibitor of growth 5 (ING5) has been reported to be involved in the malignant progression of cancers. Ursolic acid (UA) has shown remarkable antitumor effects. However, its antitumor mechanisms regarding of ING5 in hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UA significantly suppressed the proliferation, anti-apoptosis, migration and invasion of HCC cells. In addition, ING5 expression in HCC cells treated with UA was obviously downregulated in a concentration- and time-dependent manner. Additionally, the pro-oncogenic role of ING5 was confirmed in HCC cells. Further investigation revealed that UA exerted antitumor effects on HCC by inhibiting ING5-mediated activation of PI3K/Akt pathway. Notably, UA could also reverse sorafenib resistance of HCC cells by suppressing the ING5-ACC1/ACLY-lipid droplets (LDs) axis. UA abrogated ING5 transcription and downregulated its expression by reducing SRF and YY1 expression and the SRF-YY1 complex formation. Alb/JCPyV T antigen mice were used for in vivo experiments since T antigen upregulated ING5 expression by inhibiting the ubiquitin-mediated degradation and promoting the T antigen-SRF-YY1-ING5 complex-associated transcription. UA suppressed JCPyV T antigen-induced spontaneous HCC through inhibiting ING5-mediated PI3K/Akt signaling pathway. These findings suggest that UA has the dual antitumoral functions of inhibiting hepatocellular carcinogenesis and reversing sorafenib resistance of HCC cells through targeting ING5, which could serve as a potential therapeutic strategy for HCC. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).) |
| Databáze: | MEDLINE |
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