Silencing of herg gene by shRNA inhibits SH-SY5Y cell growth in vitro and in vivo.
Overexpression of human ether-à-go-go (eag) related gene (herg) contributes to the progression and metastasis of a variety of tumors of different histogenesis, which implies that the herg gene could provide a promising target on tumor therapy. In the present study, plasmid-mediated expression of shRNA-herg1 and shRNA-herg1/1b was employed to silence the herg gene expression in human neuroblastoma SH-SY5Y cell lines. The inhibition of the target gene expression was confirmed by RT-PCR and Western blot. It was found that shRNA-herg1 or shRNA-herg1/1b depressed the cellular growth rate, inhibited cell viability and reduced colony formation of SH-SY5Y cells. The flow cytometry assay revealed that SH-SY5Y cells were retarded in G0-G1 after herg1 or herg1/1b gene was silenced by shRNA-herg1 or shRNA-herg1/1b. In vivo, intra-tumor injection of shRNA-herg1/1b inhibited the growth of SH-SY5Y tumors inoculated subcutaneously in nude mice. The result suggested that the herg played an important role in regulating the growth and proliferation of SH-SY5Y cells. The block of the HERG channel might be a potential therapeutic strategy for neuroblastoma and some other tumors with overexpression of the herg gene.
Zhao
Jie
J
Beijing Institute of Pharmacology and Toxicology, Taiping Road 27, Beijing 100850, China.
Wei
Xiao-Li
XL
Jia
Yong-Sheng
YS
Zheng
Jian-Quan
JQ
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000378:metabolism; D010957:Plasmids; D012313:RNA / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051638:Ether-A-Go-Go Potassium Channels; D012313:RNA