Abstract
Purpose: To investigate the hepatoprotective role of ganoderic acid A (GAA) on liver cancer induced by diethylnitrosamine (DEN) via Nrf-2/HO-1/NF-κB signal pathway in mice.
 Methods: Sixty male C57BL/6J mice were randomly divided into 4 groups: (1) control group, (2) DEN (25 mg/kg) group, (3) GAA (20 mg/kg) + DEN group, (4) GAA (40 mg/kg) + DEN group. The protective effect of GAA on liver was evaluated by determining malondialdehyde (MDA), superoxide dismutase (SOD), inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the expression of heme oxygenase-1 (HO-1), nuclear factor erythroid- 2-related factor-2 (Nrf-2), IκBα, p-IκBα, p65, p-p65, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in serum.
 Results: The results demonstrate that GAA treatment significantly suppressed the generation of MDA, proinflammatory cytokines, and restored the activity of SOD in the serum of DEN-induced liver cancer in mice. Western blots analysis revealed that GAA significantly restored Nrf-2/HO-1/NF-κB signal pathwayrelated protein levels in DEN-induced mice liver cancer model.
 Conclusion: This research reveals the anticancer activity of GAA in liver tissue, and suggests that GAA counters DEN-induced liver cancer through Nrf-2/HO-1/NF-κB signal pathway.
 Keywords: Ganoderic acid A, Nrf-2/HO-1/NF-κB pathway, Liver cancer, MDA, GAPDH, SOD
Highlights
In recent years, hepatocellular carcinoma (HCC) has been the sixth most common form of hepatic malignancy and the third leading cause of cancer-related mortality around the world [1]
The level of MDA in serum was significantly increased in DEN-induced mice compared with control group
The level of superoxide dismutase (SOD) was significantly decreased in DEN-induced mice compared with control group
Summary
Hepatocellular carcinoma (HCC) has been the sixth most common form of hepatic malignancy and the third leading cause of cancer-related mortality around the world [1]. Diethylnitrosamine (DEN)caused hepatocellular carcinoma (HCC) in mice is one of most widely used animal models to simulate human liver cancer. The role of GAA on DEN-induced mice liver cancer and the potential mechanism were explored. As a downstream molecule of Nrf-2, over-expression of HO-1 attenuated ROS generation, modulating oxidative stress and anti-cancer effects [9]. Inhibition of Keap-1, NF-κB and induction of Nrf-2, HO-1 appear to be a potential therapeutic approach in mice liver cancer induced by DEN. Ganoderic acid A inhibits tumor growth by inducing apoptosis, this study is to explore whether or how the Nrf-2/HO-1/NF-κB signal pathway participant in anti-oxidative and antiinflammatory effects of GAA. GAA might play a key role in attenuating oxidative stress and inflammation through Nrf-2/HO-1/NFκB signaling pathway in mice liver cancer.
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