The preventative effect of Akt knockout on liver cancer through modulating NF-κB-regulated inflammation and Bad-related apoptosis signaling pathway

Primary liver cancer is globally the sixth most frequent cancer, and the second leading cause of cancer death and its incidence is increasing in many countries, thus, becoming serious threat to human health. Substantial research has focused on the treatment and prevention of liver cancer. However, the underlying molecular mechanism of liver cancer are still not fully understood, and therefore development of treatments are delayed. Akt has been suggested to play an essential role in the progression of inflammation response and apoptosis. Hence, in the present study, Akt knockout mice and cell lines were used as a model to investigate the molecular mechanism of Akt-associated inflammatory and apoptotic signaling pathway with NF-kappa B and Bad in the progression of liver cancer. Western blotting, quantitative RT-PCR (qRT-PCR), immunohistochemistry, ELISA and flow cytometric analysis were used to determine the key signaling pathway in the development of liver cancer. The results indicated that, compared to the normal liver cells, the expression of Akt was significantly higher in liver cancer cell lines. In addition, Akt-knockout liver cancer cells showed lower Akt expression. we also, found that Akt-knockout cancer cell lines modulated inflammation response and apoptosis via inhibiting NF-kappa B expression and suppressing apoptotic activation. Our results indicated that the downstream signals, including cytokines regulated by NF-kappa B signaling pathway and caspase-3-activated apoptosis affected by Bad were downregulated for knockout of Akt. These findings demonstrated that Akt is related to NF-kappa B and Bad signaling pathway possibly playing a direct role in the progression of liver cancer. Thus, Akt might be an important and potential treatment choice for the clinical diagnosis and treatment in the future.