Xie Chuangao, Xu Xuanfu, Wang Xingpeng, Wei Shumei, Shao Liming, Chen Jiamin, Cai Jianting, Jia Litao
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.
Oncol Lett. 2018 Jul;16(1):940-948. doi: 10.3892/ol.2018.8786. Epub 2018 May 22.
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 E (PGE) in pancreatic cancer and , 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). analysis was performed using ELISA or radioimmunoassay (RIA). The effect of exogenous PGE on the downregulation of VEGF by Celebrex was also assessed. 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 study indicated that Celebrex suppressed the expression of VEGF and PGE in PC-3 cells in a dose- and time-dependent manner, while exogenous PGE rescued the expression of VEGF, which was suppressed by Celebrex, in a dose-dependent manner. The study revealed that the administration of Celebrex to xenograft nude mice significantly inhibited the expression of VEGF and PGE. 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.
本研究的目的是阐明环氧化酶2（COX-2）对胰腺癌中血管内皮生长因子（VEGF）和前列腺素E（PGE）表达的影响，并阐明COX-2诱导胰腺癌血管生成的潜在机制。该研究分析在胰腺癌PC-3细胞系中进行。采用免疫组织化学法分析人胰腺癌组织中COX-2和VEGF的表达。使用抗IV型胶原抗体的免疫组织化学法检测血管生成，并根据微血管密度（MVD）进行计算。使用酶联免疫吸附测定（ELISA）或放射免疫测定（RIA）进行分析。还评估了外源性PGE对塞来昔布下调VEGF的影响。使用蛋白质印迹法或RIA进行分析。同时，还使用抗IV型胶原抗体的免疫组织化学法在裸鼠中研究了MVD。COX-2在胰腺癌组织中过表达，总体阳性率为87.5%。COX-2的表达与MVD之间存在正相关。该研究表明，塞来昔布以剂量和时间依赖性方式抑制PC-3细胞中VEGF和PGE的表达，而外源性PGE以剂量依赖性方式挽救了被塞来昔布抑制的VEGF的表达。该研究表明，给异种移植裸鼠施用塞来昔布可显著抑制VEGF和PGE的表达。这些数据提供了证据，表明PGE2可能是胰腺癌血管生成过程中COX-2和VEGF表达之间的重要介质。
