Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells.

Experimental & Molecular Medicine
Dong Woo KangDo Sik Min

Abstract

Rebamipide a gastroprotective drug, is clinically used for the treatment of gastric ulcers and gastritis, but its actions on gastric cancer are not clearly understood. Phospholipase D (PLD) is overexpressed in various types of cancer tissues and has been implicated as a critical factor in inflammation and carcinogenesis. However, whether rebamipide is involved in the regulation of PLD in gastric cancer cells is not known. In this study, we showed that rebamipide significantly suppressed the expression of both PLD1 and PLD2 at a transcriptional level in AGS and MKN-1 gastric cancer cells. Downregulation of PLD expression by rebamipide inhibited its enzymatic activity. In addition, rebamipide inhibited the transactivation of nuclear factor kappa B (NFkappaB), which increased PLD1 expression. Rebamipide or PLD knockdown significantly suppressed the expression of genes involved in inflammation and proliferation and inhibited the proliferation of gastric cancer cells. In conclusion, rebamipide-induced downregulation of PLD may contribute to the inhibition of inflammation and proliferation in gastric cancer.

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Citations

Jul 4, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xuqing WangJianxin Zhang
Feb 22, 2012·Biochemistry. Biokhimii︠a︡·Y S KolesnikovV S Kravets
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Oct 10, 2013·Biochemical and Biophysical Research Communications·Mi Hee ParkDo Sik Min
Aug 27, 2011·Biochemical and Biophysical Research Communications·Mi Hee Park, Do Sik Min
Jan 27, 2015·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Hironobu TsukamotoTakashi Joh
May 30, 2015·PloS One·Michael Pujari-PalmerMarjam Karlsson Ott
Jul 6, 2014·The Journal of Biological Chemistry·Dong Woo KangDo Sik Min
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Apr 30, 2016·Clinical Science·Junjie XiaoChangqing Yang
Mar 16, 2021·Terapevticheskiĭ arkhiv·D N Andreev, I V Maev

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