Division of Pulmonary and Critical Care Medicine, Department of Respiratory Care, Chang Gung Memorial Hospital, Chiayi, Taipei, Taiwan, ROC.
Oncol Rep. 2010 Dec;24(6):1605-12. doi: 10.3892/or_00001024.
The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is one of the most important components of cytokine signaling cascades. JAK-STAT signaling pathway modulates various fundamental biological processes and cancer pathogenesis. JAK-STAT is controlled by negative regulators that include suppressors of cytokine signaling (SOCS) proteins. Failure of feedback suppression by SOCS proteins may result in activated JAK-STAT signaling. Methylation-mediated silencing of SOCS3 has been reported in non-small lung cancer (NSCLC) and other human cancers. In this study, we restored SOCS3 expression using adenovirus-mediated gene transfer in NSCLC cells. Infection with a SOCS3-expressing vector inhibited the growth of lung cancer cells, with or without SOCS3 expression, at 2-3 days after infection. The growth inhibition of lung cancer cells was associated with suppressing entry into the S-phase. Restoration of SOCS3 expression induced apoptosis of NSCLC cells that did not express SOCS3. In addition, overexpression of SOCS3 by adenoviral transfer enhanced the radiosensitivity of treated NSCLC cells. In conclusion, our findings may provide insights into the development of applications of SOCS3 gene therapy for lung cancer and, possibly, other human cancers.
Janus 激酶-信号转导子和转录激活子（JAK-STAT）通路是细胞因子信号级联反应最重要的组成部分之一。JAK-STAT 信号通路调节各种基本的生物过程和癌症的发病机制。JAK-STAT 受到负调节因子的控制，包括细胞因子信号抑制物（SOCS）蛋白。SOCS 蛋白的反馈抑制失败可能导致 JAK-STAT 信号的激活。SOCS3 的甲基化介导的沉默已在非小细胞肺癌（NSCLC）和其他人类癌症中报道。在这项研究中，我们使用腺病毒介导的基因转移在 NSCLC 细胞中恢复 SOCS3 的表达。在感染后 2-3 天，感染 SOCS3 表达载体的肺癌细胞的生长被抑制，无论是否表达 SOCS3。肺癌细胞生长的抑制与抑制进入 S 期有关。SOCS3 表达的恢复诱导不表达 SOCS3 的 NSCLC 细胞凋亡。此外，通过腺病毒转染过表达 SOCS3 增强了治疗的 NSCLC 细胞的放射敏感性。总之，我们的研究结果可能为 SOCS3 基因治疗在肺癌和可能其他人类癌症中的应用提供新的见解。
