The potent inhibitory effects of cisapride, a specific blocker for human ether-a-go-go-related gene (HERG) channel, on gastric cancer cells.
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.
Shao
Xiao-Dong
XD
Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wu
Kai-Chun
KC
Hao
Zhi-Ming
ZM
Hong
Liu
L
Zhang
Jing
J
Fan
Dai-Ming
DM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D020117:Cisapride / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013274:Stomach Neoplasms / Q000737:chemistry / Q000378:metabolism*
D000970:Antineoplastic Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D020117:Cisapride