Reduction of p38 mitogen-activated protein kinase and cyclooxygenase-2 signaling by isoflurane inhibits proliferation and apoptosis evasion in human papillomavirus-infected laryngeal papillomas

Ren,Hongbo; Shi,Xiaojuan; Li,Ying

doi:10.3892/etm.2016.3776

Reduction of p38 mitogen-activated protein kinase and cyclooxygenase-2 signaling by isoflurane inhibits proliferation and apoptosis evasion in human papillomavirus-infected laryngeal papillomas

Authors:
- Hongbo Ren
- Xiaojuan Shi
- Ying Li
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Affiliations: Department of Otolaryngology, Children's Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China, Department of Pediatrics, Women and Infants Hospital of Zhengzhou, Zhengzhou, Henan 450012, P.R. China
Published online on: October 4, 2016 https://doi.org/10.3892/etm.2016.3776
Pages: 3425-3432

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Abstract

Human laryngeal papilloma (LP) is a human papillomavirus-induced hyperplastic tumor of the respiratory tract, which is characterized by rapid growth and apoptosis resistance. Isoflurane (ISO) inhibits proliferation and elicits apoptosis in cancer cells. The results of the present study found that the mRNA and protein levels of cyclooxygenase‑2 (COX2) were higher in LP tissues than in normal laryngeal samples, and prostaglandin E2 (PGE2) production was increased in LP cells, as determined by quantitative polymerase chain reaction, western blot and radioimmunoassay analyses. Notably, the increase in COX2 and PGE2 levels was significantly abrogated in the ISO‑treated LP cells. The inhibitory effects of ISO on COX2 expression and activity depended on the inactivation of p38 mitogen‑activated protein kinase (MAPK) in LP cells. By inhibiting the COX2 activity of LP cells, ISO treatment markedly suppressed cell viability and proliferation, as determined using Cell Counting Kit‑8, flow cytometry and 5‑ethynyl‑20‑deoxyuridine incorporation assays. Furthermore, ISO treatment promoted cell apoptosis, as demonstrated by flow cytometry, nucleosomal fragmentation and caspase‑3 activity assays. Collectively, the present results suggest that COX2 is critical in the progression of LP, and ISO is a potential agent for LP therapy by impeding p38 MAPK/COX2 signaling.

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