[Antitumor research on mouse melanoma with combined application of Newcastle disease virus and its HN gene].
OBJECTIVE
Although Newcastle disease virus (NDV) shows antitumor effect on many tumors, its mechanism is unclear. Hemagglutinin-neuraminidase (HN) gene was found to play an important role in NDV antitumor effect and HN protein located on tumor cell surface. This research was to evaluate the possibility of HN protein as a foreign antigen of tumor cell and the antitumor effect of the combined application of HN gene and NDV.


METHODS
C57BL/6 mice were subcutaneously inoculated with 2 x 10(5) B16 tumor cells in the right hindlimb. Combination group: on 2nd day post-inoculation, the recombinant plasmid containing HN gene was injected intramuscularly in the left hindlimb; on 7th day post-inoculation, 2 x 10(9) pfu NDV was administrated intratumorally. The alone HN gene group, NDV group, and PBS control group were treated as above. The antitumor effect was observed through tumor suppression rate, the antitumor mechanisms were researched with specific cytotoxic T lymphocyte (CTL) assay, and the expression determination of HN protein, ICAM-I, and CD48 on the B16 tumor cells.


RESULTS
The antitumor efficacy of the combined application of NDV and its HN gene increased compared with NDV,and its HN gene alone, the tumor suppression rates were 82.8%, 41.0%, and 56.6%; the specific CTL activity were 18.4%, 10.1%, and 4.4%, respectively. Furthermore, the expression of HN gene had been detected, and the expression of ICAM-I and CD48 were up-regulated on the tumor cells after NDV injection.


CONCLUSIONS
HN protein located on the surface of tumor cells and mediated the specific repulsion to tumor cells; the antitumor efficacy increased after the combined application of NDV and its HN gene.
Key Genetic Engineering Laboratory of PLA, Quartermaster University of PLA, Changchun, Jilin,130062, PR China.
Zhi-Qiang
ZQ
Mi
Ning-Yi
NY
Jin
Ying-Chun
YC
Sun
Xiao
X
Li
Hai
H
Lian
Jie
J
Li
Guo-Fang
GF
Guan
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism; D000071178:CD48 Antigen; D003602:Cytotoxicity, Immunologic; D015707:HN Protein / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009522:Newcastle disease virus / Q000235:genetics / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000954:Antigens, Surface; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D015707:HN Protein; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1