ONCOmmunity

SOCS1 Gene Therapy for Head and Neck Cancers: An Experimental Study.

By: Taihei Kajiyama, Satoshi Serada, Minoru Fujimoto, Tomoharu Ohkawara, Masahiro Komori, Masamitsu Hyodo, Tetsuji Naka

Department of Otolaryngology, Kochi Medical School, Kochi University, Nankoku, Japan.
2022-05-12; doi: 10.21873/anticanres.15823

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

We used cell lines of oropharyngeal and tongue cancers (Detroit-562 and SCC-9, respectively) and a recombinant adenovirus vector expressing SOCS1 (AdSOCS1).

Results

AdSOCS1-induced SOCS1 overexpression significantly decreased cell proliferation through G₂M phase cell cycle arrest and apoptosis. AdSOCS1 inhibited cell growth more strongly in SCC-9 cells than in Detroit-562 cells. JAK inhibitor I induced cell cycle arrest at the G₀/G₁ 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.