Background and goals
Despite developments in diagnostic and therapeutic strategies, hepatocellular carcinoma (HCC) remains the leading cause of cancer -related mortality. Antioxidant-1 (ATOX1) has been involved in oncogenic processes in various types of cancer. However, his particular role in HCC remains unclear. This study aims to investigate the operation of ATOX1 and its underlying molecular mechanisms in HCC.
Method
Immunohistochemical analysis was carried out to assess Atox1 expression in HCC tissues. Cell measurement kit, colonial formation, Transwell migration, flow cytometry and reactive oxygen species (ROS) were used to evaluate malignant behaviors of tumor cells. A mouse model was used to evaluate the effects of Knockdown Atox1 on volume development in vivo. DCAC50 treatment was performed to inhibit Atox1 copper transfer function. The RNA sequence was conducted to investigate the potential Molecular mechanisms of ATOX1 in HCC.
Results
Atox1 expression was significantly increased in HCC tissue. ATOX1 promoted cell proliferation, colonial formation and migration. Atox1’s knockdown has suppressed tumor growth in vivo. Mechanically, Atox1 activated C-MYB and thus enhanced the malignant phenotype of HCC cells by activating the PI3K/AKT signaling road. In addition, ATOX1 reduced the accumulation of intracellular copper and suspended ROS production and apoptosis. The inhibition of ATOX1 with DCAC50 reduced cell proliferation, while increasing ROS levels and apoptosis in HCC cells. Specifically, acetylcysteine overturned the decrease in the C-MYB expression induced by Knockdown Atox1.
Conclusions
This study states that ATOX1 promotes HCC carcinogenesis via C-MYB/PI3K/AKT signaling while inhibiting copper accumulation, ROS production and apoptosis. These results indicate that ATOX1 represents a potential therapeutic target for HCC. In addition, the DCAC50 Union, preventing the Atox1 copper transfer function, effectively suppresses the malignant behavior of HCC cells, indicating its promising role in HCC therapy, especially when combined with PI3K/AKT inhibitors.
Source:
Magazine report:
Ouyang, q., et al. (2025). ATOX1 promotes carcinogenesis carcinogenesis of hepatocellular carcinoma by activating C-MYB/PI3K/AKT signaling. Newspaper of clinical and translational hepatology. doi.org/10.14218/jcth.2024.00422.
