Exp Mol Med.  2010 Aug;42(8):555-564. 10.3858/emm.2010.42.8.056.

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

• Kang DW
• Min G
• Park DY
• Hong KW
• Min DS

• KMID: 1104382
• DOI: http://doi.org/10.3858/emm.2010.42.8.056

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.

Keyword

cell proliferation; gene expression regulation, neoplastic; inflammation; phospholipase D; rebamipide; stomach neoplasms

MeSH Terms

Alanine/*analogs & derivatives/pharmacology
Cell Line, Tumor
Cell Proliferation/drug effects
Down-Regulation/*drug effects
Gene Expression Regulation, Neoplastic/*drug effects
Humans
Inflammation/*enzymology/genetics/pathology
Isoenzymes/genetics/metabolism
NF-kappa B/metabolism
Phospholipase D/*genetics/metabolism
Promoter Regions, Genetic/genetics
Quinolones/*pharmacology
Stomach Neoplasms/*enzymology/genetics/*pathology
Transcription, Genetic/drug effects