Inhibition Effect of Ad-FGF-Trap on Head and Neck Squamous Cell Carcinoma Cells and Its Combination Therapy with Cetuximab
XIE Yuqiong1, LI Chunchun1, XIN Yongping1, YU Meirong1, LI Yi1, YAN Maoxiao2*, CAO Jiang1*
The bypass activation of FGFR1 (fibroblast growth factor receptor 1) is one of the major reasons for the common resistance to Cetuximab in the treatment of HNSCC (head and neck squamous cell carcinoma). “Decoy receptor” may have advantages over small molecule inhibitor in FGFR1 inactivation with regard to side effects. In this work, a recombinant shuttle plasmid pDC316-FGFR1 Ig2+Ig3 was constructed by genetic engineering for the expression of “Decoy receptor”. High-titer recombinant adenovirus Ad-FGF-Trap was obtained after packaging, amplification and purification using AdMaxTM adenovirus system. The proliferation, migration, invasion of human HNSCC cells CAL 27 and WSU-HN6 were significantly inhibited by infection of Ad-FGF-Trap. Apoptosis of CAL 27 cells occurred when treated with Ad-FGF-Trap, accompanied by down-regulation of PI3K/MAPK signaling pathway and up-regulation of cleaved PARP. G1/S-arrest was observed for WSU-HN6 cells treated with Ad-FGF-Trap, accompanied with up-regulation of cyclin-dependent proteins p27, p53 and PCNA, whereas enhanced compensatory activation of EGFR pathway. Ad-FGF-Trap inhibited tumor growth of CAL 27 xenografts in nude mice in vivo. Furthermore, Ad-FGF-Trap combined with Cetuximab more effectively inhibited the proliferation of WSU-HN6 cells which had high FGFR1 and EGFR expression. The current study of “decoy receptor”-expressing Ad-FGF-Trap provides a new strategy for the targeted therapy of HNSCC.
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