Apoptotic induction of lung adenocarcinoma A549 cells infected by recombinant RVG Newcastle disease virus (rL‑RVG) in vitro

Yan,Yulan; Liang,Bing; Zhang,Jin; Liu,Yang; Bu,Xuefeng

doi:10.3892/mmr.2014.2657

Apoptotic induction of lung adenocarcinoma A549 cells infected by recombinant RVG Newcastle disease virus (rL‑RVG) in vitro

Authors:
- Yulan Yan
- Bing Liang
- Jin Zhang
- Yang Liu
- Xuefeng Bu
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Affiliations: Department of Respiratory Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Department of Internal Medicine, Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China
Published online on: October 15, 2014 https://doi.org/10.3892/mmr.2014.2657
Pages: 317-326

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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.

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