Laboratory for Immune Signal, National Institute of Biomedical Innovation, Osaka, Japan.
Int J Cancer. 2011 Aug 15;129(4):1005-17. doi: 10.1002/ijc.25716. Epub 2010 Dec 2.
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis for which an effective therapy remains to be established. Our study investigated the therapeutic potential of the suppressor of cytokine signaling 3 (SOCS3), an endogenous inhibitor of intracellular signaling pathways, for treatment of MPM. We infected MPM cells (H226, EHMES-1, MESO-1 and MESO-4) with an adenovirus-expressing SOCS3 (AdSOCS3) to examine the effect of SOCS3 overexpression on MPM cells. SOCS3 overexpression reduced MPM proliferation and induced apoptosis and partial G0/G1 arrest. SOCS3 also inhibited the proliferation of MPM cells via multiple signaling pathways including Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK), focal adhesion kinase (FAK) and p53 pathways. Notably, AdSOCS3 treatment inhibited tumor growth in an MPM pleural xenograft model. These findings demonstrate that overexpression of SOCS3 has a potent antitumor effect against MPM both in vitro and in vivo and indicate the potential for clinical use of SOCS3 for MPM treatment.
恶性胸膜间皮瘤（MPM）是一种侵袭性肿瘤，预后较差，目前仍需要建立有效的治疗方法。我们的研究调查了细胞内信号通路内源性抑制剂抑制因子信号转导 3（SOCS3）在治疗 MPM 中的治疗潜力。我们用表达 SOCS3 的腺病毒（AdSOCS3）感染 MPM 细胞（H226、EHMES-1、MESO-1 和 MESO-4），以研究 SOCS3 过表达对 MPM 细胞的影响。SOCS3 过表达降低了 MPM 的增殖，并诱导了细胞凋亡和部分 G0/G1 期阻滞。SOCS3 还通过多种信号通路，包括 Janus 激酶（JAK）/信号转导和转录激活因子 3（STAT3）、细胞外信号调节激酶（ERK）、黏着斑激酶（FAK）和 p53 通路，抑制了 MPM 细胞的增殖。值得注意的是，AdSOCS3 治疗抑制了 MPM 胸膜异种移植模型中的肿瘤生长。这些发现表明，SOCS3 的过表达对 MPM 具有强大的体内外抗肿瘤作用，并表明 SOCS3 用于 MPM 治疗的临床应用潜力。
