Hypoxia promotes the migration and invasion of human hepatocarcinoma cells through the HIF-1α–IL-8–Akt axis

Maoyun Fei, Jianming Guan, Tao Xue, Lianjin Qin, Chengwu Tang, Ge Cui, Yao Wang, Hui Gong, Wenming Feng

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. The 5-year survival rate remains low despite considerable research into treatments of HCC, including surgery, radiotherapy and chemotherapy. Many mechanisms within HCC still require investigation, including the influence of hypoxia, which has a crucial role in many cancers and is associated with metastasis. Hypoxia inducible factor-1α (HIF-1α) is known to regulate the expression of many chemokines, including interleukin-8 (IL-8), which is associated with tumor metastasis. Although many studies have reported that HIF-1α is associated with HCC migration and invasion, the underlying mechanisms remain unknown. The expression level of HIF-1α was determined in HCC cells. The correlation of IL-8 and HIF-1α expressions was assessed via knockdown of HIF-1α. HCC cells were also used to assess the influence of HIF-1α on HCC cell migration and invasion. LY294002, an inhibitor of the Akt pathway, was used to confirm the associated signaling pathways. We observed a significant attenuation of cell migration and invasion after silencing of HIF-1α. Exogenously expressing IL-8 restored migration and invasion. Akt was found to be involved in this process. Hypoxia promotes HCC cell migration and invasion through the HIF-1α-IL-8-Akt axis.