Targeting HIF1α peri-operatively increased post-surgery survival in a tongue cancer animal model

Abstract

The purpose of the present study was to evaluate the relationship between hypoxia-inducible factor 1 alpha subunit (HIF1 alpha) and tumor initiation in squamous cell carcinoma cell lines and whether targeting HIF1 alpha perioperatively might exert positive effects on survival or recurrence in an animal model. The expression of HIF1 alpha and tumorigenic potential in nude mice was compared using human head and neck squamous cell carcinoma cell lines (SNU1041, SNU1066, SNU1076, PCI01, PCI13, PCI50). A recurrent tongue cancer model was established by first injecting tumor cells in the lateral tongue and then excising the tongue masses for replanting in the neck. The effect of HIF1 alpha inhibitors was assessed using this animal model. We observed good correlation between tumorigenic potential and HIF1 alpha nuclear expression in the cell lines tested. Furthermore, knockdown of HIF1 alpha inhibited tumor growth in the animal model. After in vitro testing of five HIF1 alpha inhibitors, echinomycin and LAQ824 were selected for the animal study. Pre- and postoperative treatment with echinomycin showed significant improvement in postsurgery survival and recurrence. Our results suggested that adjuvant targeting of HIF1 alpha before and after surgery could be a new targeted therapy strategy for squamous cell carcinoma.