Abstract 3740: Antitumor effect of gene therapy with SOCS-1 in esophageal squamous cell carcinoma
Authors: Takahito Sugase, Tsuyoshi Takahashi, Serada Satoshi, Eri Nakatsuka, Minoru Fujimoto, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Tetsuji Naka
Journal: Cancer Research (2016)

Abstract [INTRODUCTION] Esophageal squamous cell carcinoma (ESCC) is the major histological form of esophageal cancer in East Asian countries. Despite improvements of multimodality treatment, including surgery, radiotherapy and chemotherapy, the prognosis for patients with ESCC remains unsatisfactory compared to other cancer. Therefore, development of novel therapy is urgently required. Constitutive activation of JAK/STAT pathway has been reported in various tumor including ESCC, and associated with progression of tumor. Suppressor of cytokine signaling-1 (SOCS-1) has been cloned as a negative regulator of various cytokine signaling including JAK/STAT pathway. Recently, lines of evidences suggest that overexpression of SOCS-1 has been a promising therapeutic approach for various cancer. This study was aimed to evaluate the therapeutic effect of ESCC using SOCS-1 overexpressed by adenoviral vector (AdSOCS-1). [METHODS] For ten ESCC cell line, we evaluated cell growth inhibition via adenotransfection with various dose of AdSOCS-1 by WST-8 assay and Western blotting. Induction of apoptosis was also evaluated. In addition, it was also compared to AdSOCS-1 and JAK inhibitor for antiprolificative effect. To evaluate the therapeutic efficacy of AdSOCS-1, ESCC cell line (TE-14) was subcutaneously implanted into the ICR nu/nu mice. In addition, patient-derived tumor xenografts (PDX) using human ESCC subcutaneously transplanted in NOD-SCID mice were also assessed. Mice were intra-tumorally injection with AdSOCS-1 or control adenovirus vector (AdLacZ) twice a week for 4weeks. [RESULTS] AdSOCS-1 markedly suppressed proliferation of all ESCC cell lines in vitro. AdSOCS-1 strongly induced apoptosis via inhibiting not only JAK/STAT pathway but also MAPK and FAK signaling, especially in TE14 which was not significantly suppressed in JAK inhibitor. In TE14 xenograft model, the volume of tumors with AdSOCS-1 therapy was significantly lower than that with AdLacZ. Also, in PDX mice, injection with AdSOCS-1 significantly inhibited the tumor growth compared to AdLacZ. [CONCLUSIONS] Our results indicated that overexpression of SOCS-1 inhibited the progression of ESCC both in cell lines and xenograft model mice. Gene therapy by SOCS-1 can be a promising novel approach for intra-lesional therapy in ESCC. Citation Format: Takahito Sugase, Tsuyoshi Takahashi, Serada Satoshi, Eri Nakatsuka, Minoru Fujimoto, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Tetsuji Naka. Antitumor effect of gene therapy with SOCS-1 in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3740.