New gene therapy for lung cancer by suppressor of cytokine signaling-1

背景：JAK/STAT通路异常激活信号转导和转录激活因子(STAT)3直接参与了血液系统和非血液系统肿瘤的发生。目的：探讨SOCS-1在恶性间皮瘤发病机制中的作用。Western印迹分析检测STAT3蛋白酪氨酸磷酸化状态。Northern印迹分析检测SOCS-1mRNA的表达水平。结果：5株间皮瘤细胞系中有3株SOCS-1基因表达下调，STAT3酪氨酸磷酸化。结论：SOCS-1表达水平的降低可能导致STAT3的异常激活，SOCS-1的修复可能成为恶性间皮瘤治疗的新策略。

Background : Aberrant activation of signal transducer and activator of transcription (STAT) 3 via abnormal signaling of the Janus kinase (JAK)/STAT pathway has been demonstrated to directly contribute to oncogenesis in hematologic and non-hematologic malignancies. Loss of SOCS-1, a negative regulator of JAK/STAT pathway, has been reported to lead to STAT3 activation and cell proliferation.Objective : We examined role of SOCS-1 in the pathogenesis of malignant mesothelioma.Methods : We used five malignant mesothelioma cell lines. Western blot analysis was performed to detect tyrosine phosphorylation status of STAT3. Northern blot analysis was used to detect expression level of SOCS-1 mRNA. SOCS-1 gene was transfected to the cell lines using adenovirus vector.Results : Both tyrosine phosphorylated STAT3 and decreased expression of SOCS-1 mRNA were observed in three of five mesothelioma cell lines. The effect of SOCS-1 restoration was tested in these three cell lines and significant decrease of growth rate was observed in two of three cell lines.Conclusion : These results suggested that decreased levels of SOCS-1 expression may lead to aberrant activation of STAT3 and that the restoration of SOCS-1 may be a new therapeutic strategy for the treatment of malignant mesothelioma.