Digestive Diseases and Sciences

, Volume 52, Issue 1, pp 240–247 | Cite as

Rebamipide Inhibits Gastric Cancer Cell Growth

  • Tetsuya Tanigawa
  • Rama Pai
  • Tetsuo Arakawa
  • Andrzej S. Tarnawski
Original Paper


Rebamipide is an antiulcer drug used in Japan, Korea, China, Philippines, and other Asian countries for treatment of gastritis and peptic ulcer. Its effect on gastric cancer cell growth and its regulatory mechanisms remain unknown. We examined whether rebamipide affects human gastric cancer cell proliferation and activation of Smad signaling pathway. Gastric cancer (AGS) cells were treated with either (a) medium (control), (b) medium-containing rebamipide (0.5–2 mg/mL), or (c) PD98059+rebamipide. We determined cell proliferation, expression of p21, phosphorylation of ERK2, JNK p38, and Smad2/3, formation of Smad2/3–Smad4 complex, and nuclear translocation of Smad2/3. Rebamipide treatment inhibited AGS cell proliferation and increased p21, Smad2/3 phosphorylation, and Smad2/3–Smad4 complex formation. Rebamipide induced phosphorylation of ERK2 but not JNK or p38. Inactivation of ERK2 by PD98059 partly attenuated rebamipide-induced p21 expression. These data demonstrate that rebamipide activates Smad signaling pathway and suppresses human gastric cancer cell growth. Inactivation of ERK2 partly inhibited rebamipide-induced p21 expression, indicating a crosstalk between ERK and Smad signaling pathways.


Gastric cancer Rebamipide Cyclin-dependent kinases Smad signaling pathway MAP kinase 


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Tetsuya Tanigawa
    • 1
    • 2
    • 3
  • Rama Pai
    • 1
    • 2
  • Tetsuo Arakawa
    • 3
  • Andrzej S. Tarnawski
    • 1
    • 2
    • 4
  1. 1.Medical ServiceDepartment of Veterans Affairs Medical CenterLong BeachUSA
  2. 2.Department of MedicineUniversity of CaliforniaIrvineUSA
  3. 3.Department of GastroenterologyOsaka City University Graduate School of MedicineOsakaJapan
  4. 4.Division of GastroenterologyUniversity of California, Irvine, Chief, Gastroenterology Section (111G), DVA Medical CenterLong BeachUSA

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