Cyclooxygenase‑2 induces angiogenesis in pancreatic cancer mediated by prostaglandin E2

Xie,Chuangao; Xu,Xuanfu; Wang,Xingpeng; Wei,Shumei; Shao,Liming; Chen,Jiamin; Cai,Jianting; Jia,Litao

doi:10.3892/ol.2018.8786

Cyclooxygenase‑2 induces angiogenesis in pancreatic cancer mediated by prostaglandin E2

Authors:
- Chuangao Xie
- Xuanfu Xu
- Xingpeng Wang
- Shumei Wei
- Liming Shao
- Jiamin Chen
- Jianting Cai
- Litao Jia
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Gastroenterology, The Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Shanghai Jiaotong University, Shanghai 201620, P.R. China, Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: May 22, 2018 https://doi.org/10.3892/ol.2018.8786
Pages: 940-948
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the present study was to elucidate the effects of cyclooxygenase 2 (COX‑2) on the expression of vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) in pancreatic cancer in vitro and in vivo, and to clarify the potential mechanism of COX‑2‑induced angiogenesis of pancreatic cancer. The study analysis was conducted in the pancreatic cancer PC‑3 cell line. The expression of COX‑2 and VEGF in human pancreatic cancer tissue was analyzed by immunohistochemistry. Angiogenesis was detected using immunohistochemistry with anti‑collagen IV antibodies, and was calculated according to the microvascular density (MVD). In vitro analysis was performed using ELISA or radioimmunoassay (RIA). The effect of exogenous PGE2 on the downregulation of VEGF by Celebrex was also assessed. In vivo analysis was performed using western blotting or RIA. Concurrently, MVD was also investigated in nude mice using immunohistochemistry with anti‑collagen IV antibodies. COX‑2 was overexpressed in pancreatic cancer tissues, with an overall positive rate of 87.5%. There was a positive association between the expression of COX‑2 and MVD. The in vitro study indicated that Celebrex suppressed the expression of VEGF and PGE2 in PC‑3 cells in a dose‑ and time‑dependent manner, while exogenous PGE2 rescued the expression of VEGF, which was suppressed by Celebrex, in a dose‑dependent manner. The in vivo study revealed that the administration of Celebrex to xenograft nude mice significantly inhibited the expression of VEGF and PGE2. These data provide evidence that PGE2 may be an important mediator between COX‑2 and VEGF expression in the process of angiogenesis in pancreatic cancer.

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