Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells.
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.
Kang
Dong Woo
DW
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Korea.
Min
Gyesik
G
Park
Do Yoon
DY
Hong
Ki Whan
KW
Min
Do Sik
do S
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic / Q000187:drug effects
D007527:Isoenzymes; D016328:NF-kappa B; D015363:Quinolones; D010739:Phospholipase D; C052785:rebamipide; D000409:Alanine