SOCS1 Gene Therapy for Head and Neck Cancers: An Experimental Study
Taihei Kajiyama, Satoshi Serada, Minoru Fujimoto, Tomoharu Ohkawara, Masahiro Komori, Masamitsu Hyodo, Tetsuji Naka
Abstract
BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is a fatal and debilitating disease, which is characterized by steady, poor survival rates despite advances in treatment. Suppressor of cytokine signaling (SOCS) 1 is up-regulated following cytokine-induced Janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway activation, and inhibitors of cytokine signaling play roles in regulating cell growth and differentiation. We investigated the therapeutic potential of SOCS1 for HNSCC. MATERIALS AND METHODS: We used cell lines of oropharyngeal and tongue cancers (Detroit-562 and SCC-9, respectively) and a recombinant adenovirus vector expressing SOCS1 (AdSOCS1). RESULTS: and GfM phases in Detroit-562 and SCC-9 cells, respectively. AdSOCS1 also decreased the activity of phosph-STAT3 (pSTAT3) and phosphop44/42 mitogen-activated protein kinase (p-p44/42 MAPK), as well as the expression of the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-xL). JAK inhibitor I decreased the expression of pSTAT3, but not p-p44/42 or Bcl-xL. The MAPK/extracellular signal-regulated kinase (MEK) inhibitor, U0126, decreased the expression of Bcl-xL in SCC-9 cells, but not in Detroit-562 cells. AdSOCS1 treatment inhibited tumor growth in mouse xenograft models. CONCLUSION: Overexpression of SOCS1 has a potent antitumor effect on HNSCC, suggesting the potential for clinical use. The varying effectiveness among cancer cells by over expression of SOCS1 may contribute to efficacy of SOCS 1 gene therapy for clinical use.