Downregulation of cyclooxygenase‑1 stimulates mitochondrial apoptosis through the NF‑κB signaling pathway in colorectal cancer cells

Ding,Lei; Gu,Huan; Lan,Zhenwei; Lei,Qingchun; Wang,Wenxue; Ruan,Jiangfei; Yu,Min; Lin,Jie; Cui,Qinghua

doi:10.3892/or.2018.6785

Downregulation of cyclooxygenase‑1 stimulates mitochondrial apoptosis through the NF‑κB signaling pathway in colorectal cancer cells

Authors:
- Lei Ding
- Huan Gu
- Zhenwei Lan
- Qingchun Lei
- Wenxue Wang
- Jiangfei Ruan
- Min Yu
- Jie Lin
- Qinghua Cui
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Affiliations: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan 650091, P.R. China, Department of Neurosurgery, Pu'er City People's Hospital, Pu'er, Yunnan 66500, P.R. China, Key Laboratory of Molecular Cancer Biology, Yunnan Education Department, Kunming, Yunnan 650091, P.R. China
Published online on: October 12, 2018 https://doi.org/10.3892/or.2018.6785
Pages: 559-569

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Abstract

The prognosis of patients with colorectal cancer (CRC) remains poor owing to diagnosis typically occurring at advanced stages of the disease. The understanding of the molecular regulatory signatures of CRC may lead to the identification of biomarkers for the early detection, prevention and clinical intervention of CRC. Epidemiological studies have indicated that cyclooxygenase‑1 (COX‑1) serves an active function in colon carcinogenesis. However, the molecular mechanism underlying COX‑1 regulation in CRC remains unknown. In the present study, COX‑1 was identified to be markedly upregulated in colorectal tissues of patients with CRC, and in the CRC cell lines HCT116 and HT29. To determine the function of COX‑1 in cancer development, short hairpin RNA knockdown of COX‑1 was employed in HCT116 and HT29 CRC cells in the present study. The results demonstrated that silencing of COX‑1 depolarized the mitochondrial membrane potential, inhibited adenosine triphosphate production, induced the generation of intracellular reactive oxygen species and triggered caspase‑dependent mitochondrial apoptosis. Furthermore, depletion of COX‑1 suppressed anti‑apoptotic B‑cell lymphoma 2 and enhanced pro‑apoptotic Bcl‑2‑associated X protein expression by inhibiting the p65 subunit phosphorylation of nuclear factor κB (NF‑κB). Taken together, the results of the present study indicated that COX‑1 inhibition significantly triggered cell death by destroying the mitochondrial function that is associated with deactivation of the NF‑κB signaling pathway. These results suggest COX‑1 as a potential anticancer target in CRC.

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