Decreased expression level and DNA‑binding activity of specificity protein 1 via cyclooxygenase‑2 inhibition antagonizes radiation resistance, cell migration and invasion in radiation‑resistant lung cancer cells

Liu,Ruijun; Tan,Qiang; Luo,Qingquan

doi:10.3892/ol.2018.9035

Decreased expression level and DNA‑binding activity of specificity protein 1 via cyclooxygenase‑2 inhibition antagonizes radiation resistance, cell migration and invasion in radiation‑resistant lung cancer cells

Authors:
- Ruijun Liu
- Qiang Tan
- Qingquan Luo
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Affiliations: Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
Published online on: June 28, 2018 https://doi.org/10.3892/ol.2018.9035
Pages: 3029-3037
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiation is able to inhibit tumor growth, promote tumor cell apoptosis and prolong patient survival. However, radiation resistance remains a major impediment to radiotherapy. Local and metastatic recurrences following radiation are still large impediments to overall survival. Although cyclooxygenase‑2 (COX‑2) inhibitors may induce radiation sensitivity in cancer cells, the underlying mechanisms are not fully understood. The present study demonstrated high potential for cell proliferation, migration and invasion in radiation‑resistant lung cancer cell lines. The present study observed the overexpression of specificity protein 1 (Sp1) in these cells, and the overexpression of Sp1 induced upregulation of matrix metalloproteinase (MMP)‑2, MMP‑9, B cell lymphoma‑2, in addition to a high potential for radiation resistance, migration and invasion in these cells. The present study revealed that the COX‑2 selective inhibitor, celecoxib, enhanced radiation sensitivity and inhibited migration and invasion in these cells by inhibiting the expression and DNA‑binding activity of Sp1. Furthermore, celecoxib downregulated Sp1 by inhibiting c‑Jun N‑terminal kinase (JNK). Taken together, the present study demonstrated that Sp1 overexpression in radiation‑resistant cancer cells and COX‑2 inhibitors enhanced radiation sensitivity and inhibited the migration and invasion of cancer cells, at least partially, via inactivation of the JNK/Sp1 signaling pathway and a decrease in Sp1 DNA‑binding activity.

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