TNF‑α‑mediated upregulation of SOD‑2 contributes to cell proliferation and cisplatin resistance in esophageal squamous cell carcinoma

Zuo,Jing; Zhao,Mei; Liu,Bowei; Han,Xiaojing; Li,Yuehong; Wang,Wei; Zhang,Qing; Lv,Ping; Xing,Lingxiao; Shen,Haitao; Zhang,Xianghong

doi:10.3892/or.2019.7252

TNF‑α‑mediated upregulation of SOD‑2 contributes to cell proliferation and cisplatin resistance in esophageal squamous cell carcinoma

Authors:
- Jing Zuo
- Mei Zhao
- Bowei Liu
- Xiaojing Han
- Yuehong Li
- Wei Wang
- Qing Zhang
- Ping Lv
- Lingxiao Xing
- Haitao Shen
- Xianghong Zhang
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Affiliations: Lab of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Anesthesiology, The Central Hospital of Dandong, Dandong, Liaoning 118002, P.R. China, Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Published online on: July 26, 2019 https://doi.org/10.3892/or.2019.7252
Pages: 1497-1506

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Abstract

Intrinsic and acquired resistance of cancer to radio‑and chemotherapy is one of the major challenges in the treatment of esophageal squamous cell carcinoma (ESCC). Elevated reactive oxygen species (ROS) play an important role in the resistance to cisplatin in ESCCs. Super dismutase [Mn], mitochondrial (SOD‑2), an important primary antioxidant enzyme located in mitochondria, could regulate ROS production. Our previous study showed that tumor necrosis factor‑α (TNF‑α)‑mediated SOD‑2 through NF‑κB was involved in epithelial‑mesenchymal transition and migration in A549 cells. Therefore, the present study aimed to identify if TNF‑α mediated SOD‑2 upregulation is involved in cisplatin resistance in ESCC. It was identified that a higher expression of SOD‑2 in human ESCC samples was associated with TNF‑α expression and poor overall survival in patients with ESCC, suggesting that SOD‑2 may act as an oncogene in ESCC. To further confirm if TNF‑α could upregulate SOD‑2 to contribute to cell proliferation, the human ESCC cell line Eca‑109 was treated with TNF‑α in vitro. TNF‑α could upregulate SOD‑2 and induce cell proliferation in Eca109 cells, while blocking SOD‑2 using small interfering RNA (siRNA) inhibited TNF‑α‑induced cell proliferation. Upregulation of SOD‑2 by TNF‑α was inhibited by blocking the NF‑κB pathway, which suggested that SOD‑2 by TNF‑α/NF‑κB contributes to cell proliferation in Eca109 cells. Furthermore, it was observed that TNF‑α could induce cisplatin resistance in Eca109 cells, while transfection with SOD‑2 siRNA could significantly increase the chemosensitivity of ESCC to cisplatin. Therefore, the present results suggested that SOD‑2 may serve as an oncogene, and the upregulation of SOD‑2 by TNF‑α/NF‑κB may contribute to cisplatin resistance in ESCC.

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