title: Apoptotic induction of lung adenocarcinoma A549 cells infected by recombinant RVG Newcastle disease virus (rL-RVG) in vitro.
abstract: Newcastle disease virus (NDV) is a member of the genus Avulavirus in the Paramyxoviridae family and its antitumor properties depend on its ability to kill malignant cells while not affecting normal cells. The present study investigated a recombinant avirulent NDV LaSota strain (wild-type NDV strain) expressing the rabies virus glycoprotein (rL-RVG), examined its oncolytic effect on the lung adenocarcinoma A549 cell line and evaluated its potential to serve as a vaccine against lung cancer. A549 cells were infected with the rL-RVG virus and analyzed by MTT, western blot, polymerase chain reaction (PCR), immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling and flow-cytometric analyses. PCR, western blot and immunoﬂuorescence showed that the RVG gene and protein were stably expressed in A549 cells following infection with rL-RVG. The growth of A549 cells in the rL-RVG group was inhibited more effectively compared to those infected with the wild-type NDV strain. MTT results showed that cell growth inhibition rates in the rL-RVG group were significantly higher than those in the NDV group (P<0.05). Early apoptosis in the rL-RVG group was also more evident, with the apoptotic index being increased in rL-RVG group. The expression of the pro-apoptotic proteins caspase-3, -8 and -9 increased. The expression of caspase-3 decreased following application of the broad-speciﬁcity caspase inhibitor Z-VAD-FMK. However, the expression of the inhibitory apoptosis protein B-cell lymphoma 2 (bcl-2) did not change, but bcl-2-associated X/bcl-2 ratio was higher in the rL-RVG group than that in the NDV group. The rL-RVG strain was able to suppress lung cancer cell growth and promote lung cancer cell apoptosis to a greater extent than the wild-type NDV strain. Therefore, the rL-RVG strain is a potent antitumor agent.
authors.affiliation: Department of Respiratory Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Internal Medicine, Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Respiratory Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Bu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D009522:Newcastle disease virus / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020169:Caspases