PMID- 25202402
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 8
IP  - 4
DP  - 2014 Oct
TI  - Rabeprazole exhibits antiproliferative effects on human gastric cancer cell 
      lines.
PG  - 1739-1744
AB  - Intracellular proton extrusion in gastric cancer cells has been reported to 
      promote cancer cell survival under acidic conditions via hydrogen/potassium 
      adenosine triphosphatase (H(+)/K(+)-ATPase). Rabeprazole is a frequently used 
      second-generation proton pump inhibitor (PPI) that irreversibly inactivates 
      gastric H(+)/K(+)-ATPase. Therefore, we hypothesized that rabeprazole could 
      reduce the viability of gastric cancer cells. In the present study, four human 
      gastric cancer cell lines and one non-cancer gastric cell line were cultured. 
      Cell viability, the alpha- and beta-subunits of H(+)/K(+)-ATPase and cellular apoptosis 
      were analyzed by dye exclusion assay, reverse transcription-polymerase chain 
      reaction and annexin V-fluorescein isothiocyanate/propidium iodide staining, 
      respectively. The expression level of total extracellular signal-regulated 
      protein kinase 1/2 (ERK 1/2) and phosphorylated-ERK protein was detected by 
      western blot analysis. Gastric cancer cell lines were more tolerant of the acidic 
      culture media than non-cancer cells. Administration of rabeprazole led to a 
      marked decrease in the viability of MKN-28 cells. Exposure to rabeprazole induced 
      significant apoptosis in AGS cells. Rabeprazole completely inhibited the 
      phosphorylation of ERK 1/2 in the MKN-28 cells, whereas the same effect was not 
      observed in either the KATO III or MKN-45 cells. The ERK 1/2 inhibitor, PD98059, 
      attenuated the viability of the AGS cells. A similar antiproliferative effect was 
      observed in the rabeprazole treatment group. In addition, PD98059 and rabeprazole 
      were able to efficaciously inhibit the phosphorylation of ERK 1/2 in the gastric 
      cancer cells. Therefore, it was concluded that rabeprazole can attenuate the cell 
      viability of human gastric cancer cells through inactivation of the ERK1/2 
      signaling pathway. The results of the present study demonstrate that rabeprazole 
      inhibits the viability of gastric cancer cells in vitro and may serve as a novel 
      antineoplastic agent.
FAU - Gu, Mengli
AU  - Gu M
AD  - Department of Gastroenterology, The First Affiliated Hospital of Medical College 
      of Zhejiang University, Hangzhou, Zhejiang, P.R. China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Gastroenterology, The First Affiliated Hospital of Medical College 
      of Zhejiang University, Hangzhou, Zhejiang, P.R. China.
FAU - Zhou, Xinxin
AU  - Zhou X
AD  - Department of Gastroenterology, The First Affiliated Hospital of Medical College 
      of Zhejiang University, Hangzhou, Zhejiang, P.R. China.
FAU - Ma, Han
AU  - Ma H
AD  - Department of Gastroenterology, The First Affiliated Hospital of Medical College 
      of Zhejiang University, Hangzhou, Zhejiang, P.R. China.
FAU - Yao, Hangping
AU  - Yao H
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The 
      First Affiliated Hospital of Medical College of Zhejiang University, Hangzhou, 
      Zhejiang, P.R. China.
FAU - Ji, Feng
AU  - Ji F
AD  - Department of Gastroenterology, The First Affiliated Hospital of Medical College 
      of Zhejiang University, Hangzhou, Zhejiang, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20140716
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4156221
OTO - NOTNLM
OT  - antineoplastic therapy
OT  - extracellular signal-regulated protein kinase 1/2
OT  - gastric cancer
OT  - proton pump inhibitors
OT  - rabeprazole
EDAT- 2014/09/10 06:00
MHDA- 2014/09/10 06:01
PMCR- 2014/07/16
CRDT- 2014/09/10 06:00
PHST- 2014/01/29 00:00 [received]
PHST- 2014/07/08 00:00 [accepted]
PHST- 2014/09/10 06:00 [entrez]
PHST- 2014/09/10 06:00 [pubmed]
PHST- 2014/09/10 06:01 [medline]
PHST- 2014/07/16 00:00 [pmc-release]
AID - ol-08-04-1739 [pii]
AID - 10.3892/ol.2014.2354 [doi]
PST - ppublish
SO  - Oncol Lett. 2014 Oct;8(4):1739-1744. doi: 10.3892/ol.2014.2354. Epub 2014 Jul 16.