Effect of hypoxia-inducible factor 1-α on Survivin in colorectal cancer.

Colorectal cancer is a one of the most common malignancies. Hypoxia-inducible factor 1-α (HIF1-α) and Survivin play important roles in tumor development; however, the literature currently contains few reports on the relationship between them in colorectal cancer. In this study, we investigated the effect of HIF1-α on Survivin in colorectal cancer. Immunohistochemical staining was used to detect the expression of HIF1-α and Survivin in colorectal cancer tissue from 32 patients. Colon adenocarcinoma SW480 cells were cultured under normoxia and hypoxic conditions, and the expression of HIF1-α and Survivin was detected by RT-PCR and Western blotting. We also silenced HIF1-α in order to detect the expression of Survivin and cell apoptosis. In an in vivo xenograft tumor model, the effect of HIF1-α on cancer development and Survivin was evaluated by the measurment of tumor volume and immunohistochemical analysis. Analysis revealed that HIF1-α (75%) and Survivin (68.75%) were both overexpressed in colorectal cancer, and that their expression was correlated. They were also expressed in SW480 cells under conditions of normoxia, and exhibited a significant increase in expression under hypoxic conditions. The inhibition of HIF1-α by RNA interference decreased the expression of Survivin and led to the apoptosis of the SW480 cell line. In the in vivo xenograft tumor model, the expression of HIF1-α and Survivin was decreased in the siHIF1-α group, and the tumor volume (586.67±41.63 mm3) was much smaller than that in the negative interference (1374.67±85.87 mm3) and saline-treated (1382.80±28.42 mm3) groups. Our results indicate that HIF1-α is an important regulator of Survivin expression and has great potential capacity for cancer therapeutics.