Protease-activated receptor-2 induces expression of vascular endothelial growth factor and cyclooxygenase-2 via the mitogen-activated protein kinase pathway in gastric cancer cells

Zhang,Cheng; Gao,Guang-Rong; Lv,Chen-Guang; Zhang,Boa-Lei; Zhang,Zhi-Li; Zhang,Xue-Feng

doi:10.3892/or.2012.1998

Protease-activated receptor-2 induces expression of vascular endothelial growth factor and cyclooxygenase-2 via the mitogen-activated protein kinase pathway in gastric cancer cells

Authors:
- Cheng Zhang
- Guang-Rong Gao
- Chen-Guang Lv
- Boa-Lei Zhang
- Zhi-Li Zhang
- Xue-Feng Zhang
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Affiliations: Department of General Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110840, P.R. China
Published online on: August 30, 2012 https://doi.org/10.3892/or.2012.1998
Pages: 1917-1923

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Abstract

Protease-activated receptor-2 (PAR-2) has shown strong pro-angiogenesis activity physiologically and pathologically. This study aimed to explore PAR-2 regulation of pro-angiogenesis gene expression and the underlying molecular pathways in gastric cancer cells. MKN28 human gastric cancer cells were treated with trypsin, a PAR-2 activator, and subjected to real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting and ELISA for gene expression analyses. ERK1/2 phosphorylation and p38 MAP kinase inhibitors (PD98059 and SB203580, respectively) were used to block their gene activities. PAR-2 mRNA and protein were expressed in MKN-28 cells and activated by trypsin treatment. Trypsin-activated PAR-2 protein significantly enhanced expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) mRNA and protein in gastric cancer cells in a dose- and time-dependent manner. PAR-2 activation also induced the phosphorylation of ERK1/2 and p38 MAP kinase, but the ERK1/2 and p38 inhibitors blocked the activated PAR-2-induced VEGF and COX-2 expression in gastric cancer cells. PAR-2-induced expression of VEGF and COX-2 mRNA and protein in gastric cancer MKN28 cells was mediated by activation of an ERK1/2- and p38 MAP kinase-dependent pathway. Thus, PAR-2 may serve as a promising target for anti-angiogenesis therapy to treat gastric cancer.

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