Department of Cardiothoracic Surgery, School of Medicine, Nanjing University, Nanjing General Hospital of Nanjing Command, Nanjing, Jiangsu 210002, P.R. China.
Department of Cardiothoracic Surgery, Chenggong Hospital, Xiamen University, Xiamen, Fujian 361003, P.R. China.
Int J Mol Med. 2018 May;41(5):2961-2967. doi: 10.3892/ijmm.2018.3447. Epub 2018 Feb 1.
Tumor recurrence and metastasis in esophageal squamous cell carcinoma (ESCC) are primary causes of patient mortality. The nuclear factor (NF)‑κB signaling pathway and hedgehog signaling pathway were previously reported to contribute to cell growth and metastasis in ESCC. The present study therefore investigated the roles of the NF‑κB and hedgehog pathways in ESCC tumors following neoadjuvant chemoradiotherapy (NCRT). By immunohistochemistry staining, it was observed that NF‑κB and glioma‑associated oncogene homolog 1 (Gli1), key components of the NF‑κB and hedgehog pathways, respectively, were decreased following NCRT, which was further confirmed by western blotting and reverse transcription‑quantitative polymerase chain reaction analysis. In addition, survival analysis suggested that high expression levels of either NF‑κB or Gli1 were associated with poor overall survival (OS) of patients. In the esophageal cell line TE‑8, NF‑κB and Gli1 formed a positive feedback loop, and inhibition of either NF‑κB or Gli1 may inhibit cell migration, invasion and proliferation. The results of the present study demonstrated that activation of the NF‑κB and hedgehog signaling pathways limited the OS of patients with ESCC following NCRT, and may therefore be suitable targets for ESCC treatment.
肿瘤复发和转移是食管鳞状细胞癌（ESCC）患者死亡的主要原因。核因子（NF）-κB 信号通路和 hedgehog 信号通路先前被报道可促进 ESCC 中的细胞生长和转移。因此，本研究探讨了 NF-κB 和 hedgehog 通路在 ESCC 肿瘤接受新辅助放化疗（NCRT）后的作用。通过免疫组织化学染色观察到，NF-κB 和Gli1（ hedgehog 通路的关键组成部分）在 NCRT 后减少，这通过 Western blot 和逆转录-定量聚合酶链反应分析进一步证实。此外，生存分析表明，NF-κB 或 Gli1 的高表达水平与患者的总生存（OS）不良相关。在食管细胞系 TE-8 中，NF-κB 和 Gli1 形成正反馈回路，抑制 NF-κB 或 Gli1 中的任何一种均可抑制细胞迁移、侵袭和增殖。本研究的结果表明，NF-κB 和 hedgehog 信号通路的激活限制了接受 NCRT 的 ESCC 患者的 OS，因此可能是 ESCC 治疗的合适靶点。
