Antisense RNA to eIF4E suppresses oncogenic properties of a head and neck squamous cell carcinoma cell line

Objective: The translation initiation factor eIF4E is elevated in all head and neck squamous cell cancers (HNSCCs) and appears to be essential in the progression of solid tumors. Overexpression of eIF4E results in preferentia l upregulation of two angiogenic factors, vascular endothelial growth facto r (VEGF) and basic fibroblast growth factor (FGF-8). We wanted to determine whether reducing eIF4E in a HNSCC cell line could suppress its oncogenic p roperties and in turn decrease expression of VEGF and FGF-2, Methods: Level s of eIF4E protein expression were determined in a panel of HNSCC cell line s. An episomal vector containing antisense RNA to eIF4E was used to reduce the eIF4E level in one of these cell lines, FaDu, After a stable transfecti on, Western blot analysis was performed to determine the level of eIF4E and FGF-2 reduction, while an enzyme-linked immunosorbent assay (ELISA) was us ed to determine the level of VEGF reduction. In vitro and in vivo experimen ts were performed to determine whether there was a reversion in the tumorig enic properties of the FaDu cells. Results: All six cell lines had elevated levels of eIF4E compared with Detroit 551, a normal cell line. Reducing eI F4E expression via antisense RNA suppressed both the tumorigenic and angiog enic properties of the FaDu cells, as demonstrated by loss of capacity to g row in soft agar, reduced expression of angiogenic factors, and loss of tum origenicity in nude mice. Conclusions: Antisense RNA therapy to eIF4E can p otentially be used as adjuvant therapy for head and neck cancers, particula rly in cases in which elevated eIF4E is found in the surgical margins.