The potent inhibitory effects of cisapride, a specific blocker for human ether-a-go-go-related gene (HERG) channel, on gastric cancer cells.
Cancer Biol Ther
; 4(3): 295-301, 2005 Mar.
Article
en En
| MEDLINE
| ID: mdl-15846098
ABSTRACT
BACKGROUND:
Ion channels may play a role in carcinogenesis. Human ether-a-go-go-related gene (HERG) encoding one of the components of delayed rectifier potassium currents has been indicated to be involved in tumor cell growth and death. Our aim is to investigate the effects of cisapride, a specific blocker for HERG channel, on human gastric cancer cells.METHODS:
The effects of cisapride on the proliferation, clonogenicity, cell cycle and apoptosis of gastric cancer cells were evaluated by MTT assay, clonogenicity assay, flow cytometry and transmission electron microscopy. The expression of HERG mRNA and protein in gastric cancer cells and tissues was measured by RT-PCR, Western blot and immunohistochemistry, respectively.RESULTS:
HERG mRNA and protein were exclusively expressed in gastric cancer cells. The HERG protein was localized in the cytoplasm and membrane of the gastric cancer cells. The proliferation of gastric cancer cells expressing HERG protein was inhibited in a time- and dose-dependent manner when treated with cisapride (P<0.05). The clonogenicity of gastric cancer cells treated with cisapride (100 nM) was reduced (P<0.05). Flow cytometric analysis indicated that cisapride tends to inhibit gastric cancer cells entering S phase from G(1) phase in the cell cycle (P<0.05). Apoptotic cells were found increased in gastric cancer cells treated with cisapride by both flow cytometry and electron microscopy.CONCLUSIONS:
As HERG channel blocker, cisapride, can inhibit the growth of gastric cancer cells by altering distribution of cell cycle and inducing apoptosis so as to be of potential value in the treatment of gastric cancer.
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Colección:
01-internacional
Asunto principal:
Neoplasias Gástricas
/
Cisaprida
/
Bloqueadores de los Canales de Potasio
/
Canales de Potasio Éter-A-Go-Go
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Cancer Biol Ther
Asunto de la revista:
NEOPLASIAS
/
TERAPEUTICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
China