Inhibition of Akt/PKB by a COX-2 inhibitor induces apoptosis in gastric cancer cells

Digestion
Xiao Ming FanBenjamin Chun-Yu Wong

Abstract

Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway. Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line. SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases. One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c.

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Citations

Apr 4, 2009·Anti-cancer Drugs·Dan LiYunpeng Liu
Aug 29, 2007·Acta Pharmacologica Sinica·Fazlul H Sarkar, Yi-wei Li
Mar 29, 2014·International Journal of Molecular Medicine·Min LiuYong-Ning Zhou
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Dec 30, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hassan AkramiHossein Fallahi

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