Abstract
CONTEXT: Previous studies have demonstrated that 3'-azido-3'-deoxythymidine (AZT) and arsenic trioxide (As(2)O(3)), traditional chemotherapy agents, can synergically inhibit the growth of hepatocellular carcinoma cells. However, the molecular mechanisms underlying As(2)O(3) and AZT anti-hepatoma activity are unknown. OBJECTIVE: This study aimed to investigate the role of early growth response protein 1 (Egr-1) in the process of As(2)O(3) combined with AZT inhibiting proliferation and inducing apoptosis of human hepatocellular carcinoma HepG2 cells, and explore the possible mechanism. MATERIALS AND METHODS: The expression of Egr-1 was silenced using siRNA, and then HepG2 cells were treated with As(2)O(3) (2 μM) and AZT (20 μM). The rates of cell inhibition and apoptosis were determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) method and flow cytometry, respectively. The mRNA and protein expression of p53, caspase-3, and Egr-1 were detected by real-time quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: The inhibitory rate of As(2)O(3) (2 μM) combined with AZT (20 μM) on proliferation of HepG2 cells was significantly higher than that of As(2)O(3) alone. The combination index (CI) values were 0.2