Effect of the parvovirus H-1 non-structural protein NS1 on the tumorigenicity of human gastric cancer cells.

OBJECTIVE

To investigate the in vivo oncosuppressive effect of the non-structural protein NS1 of parvovirus H-1 on human gastric cancer cell lines.

METHODS

Recombinant plasmid pcDNA3.1-NS1 containing the complete NS1 gene of parvovirus H-1 was constructed and characterized by restriction enzyme digestion and sequence analysis. The human gastric cancer cell lines MKN28, SGC7901 and MKN45 were stably transfected with empty or recombinant plasmids. NS1 gene transcription and protein expression in the latter transfectants were verified by reverse transcriptase polymerase chain reaction and Western blot, respectively. The oncosuppressive effect of the parvoviral protein NS1 on the gastric cancer cell lines was tested by comparing the tumorigenicity of empty and recombinant vector-transfected cells in nude mice.

RESULTS

Well differentiated gastric cancer cells (MKN28) transfected with either empty plasmid or pcDNA3.1-NS1 were tumorigenic in nude mice. Moderately (SGC7901) and poorly (MKN45) differentiated gastric cancer cells transfected with empty plasmid were also tumorigenic, but no tumor resulted from the injection when they were transfected with pcDNA3.1-NS1. This NS1-associated suppression of SGC7901 and MKN45 tumors correlated with the decreased percentage of CD44 positive cells.

CONCLUSIONS

NS1 expression in poorly differentiated gastric cancer cells prevents them from forming tumors, perhaps by impairing the stem-like phenotype. The parvoviral NS1 protein warrants further investigation for its therapeutic potential against cancer.