Rabeprazole exhibits antiproliferative effects on human gastric cancer cell lines
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- Published online on: July 16, 2014 https://doi.org/10.3892/ol.2014.2354
- Pages: 1739-1744
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Abstract
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 α‑ and β‑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.
