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.
Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, China.
Yuan Yuan
YY
Wang
Jiong
J
Liu
Qing
Q
Zheng
Zhi Hua
ZH
Ran
Nathalie
N
Salomé
Michèle
M
Vogel
Jean
J
Rommelaere
Shu Dong
SD
Xiao
Zheng
Z
Wang
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014162:Transfection; D014183:Transplantation, Heterologous; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000502:physiology
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C106202:NS1 protein, parvovirus; D009363:Neoplasm Proteins; D017361:Viral Nonstructural Proteins