PT - JOURNAL ARTICLE AU - TAIHEI KAJIYAMA AU - SATOSHI SERADA AU - MINORU FUJIMOTO AU - TOMOHARU OHKAWARA AU - MASAHIRO KOMORI AU - MASAMITSU HYODO AU - TETSUJI NAKA TI - SOCS1 Gene Therapy for Head and Neck Cancers: An Experimental Study AID - 10.21873/anticanres.15823 DP - 2022 Jul 01 TA - Anticancer Research PG - 3361--3372 VI - 42 IP - 7 4099 - http://ar.iiarjournals.org/content/42/7/3361.short 4100 - http://ar.iiarjournals.org/content/42/7/3361.full SO - Anticancer Res2022 Jul 01; 42 AB - 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: 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.