Indometacin Ameliorates High Glucose-Induced Proliferation and Invasion Via Modulation of E-Cadherin in Pancreatic Cancer Cells

Author(s): Liang Han, Bo Peng, Qingyong Ma, Jiguang Ma, Juntao Li, Wei Li, Wanxing Duan, Chao Chen, Jiangbo Liu, Qinhong Xu, Kyle Laporte, Zehui Li, Erxi Wu.

Journal Name: Current Medicinal Chemistry

Volume 20 , Issue 33 , 2013

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Abstract:

Indometacin, an inhibitor of cyclooxygenase-2 (COX-2), has been shown to exert anticancer effects in a variety of cancers. However, the effect and mechanism of indometacin on high glucose (HG)-induced proliferation and invasion of pancreatic cancer (PC) cells remain unclear. Multiple lines of evidence suggest that a large portion of pancreatic cancer (PC) patients suffer from either diabetes or HG which contributing PC progression. In this study, we report that indometacin down-regulated HG-induced proliferation and invasion via up-regulating E-cadherin but not COX-2 in PC cells. Additionally, the E-cadherin transcriptional repressors, Snail and Slug, were also involved in the process. Furthermore, the proliferation and invasion of PC cells, incubated in HG medium and treated with indometacin were significantly increased when E-cadherin was knocked down (Si-E-cad). Moreover, the protein levels of MMP-2, MMP-9, and VEGF were increased in PC cells transfected with Si-E-cad. Finally, the activation of the PI3K/AKT/GSK-3β signaling pathway was demonstrated to be involved in indometacin reversing HG-induced cell proliferation and invasion in PC cells. In conclusion, these results suggest that indometacin plays a key role in down-regulating HG-induced proliferation and invasion in PC cells. Our findings indicate that indometacin could be used as a novel therapeutic strategy to treat PC patients who simultaneously suffer from diabetes or HG.

Keywords: Cancer progression, COX-2, E-cadherin, high glucose, indometacin, invasion, pancreatic cancer, PI3K/AKT, proliferation, therapeutic strategy.

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Article Details

VOLUME: 20
ISSUE: 33
Year: 2013
Page: [4142 - 4152]
Pages: 11
DOI: 10.2174/09298673113209990249
Price: $58

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