Autophagy is involved in recombinant Newcastle disease virus (rL-RVG)-induced cell death of stomach adenocarcinoma cells in vitro

Author： Bu Xu-Feng Wang Mu-Bing Zhang Zhi-Jian Zhao Ying-Hai Li Mi Yan Yu-Lan

Publisher： Spandidos Publications

E-ISSN： 1791-2423|47|2|679-689

ISSN： 1019-6439

Source： International Journal of Oncology, Vol.47, Iss.2, 2015-08, pp. : 679-689

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Abstract

Oncolytic viruses can kill malignant cells while sparing normal cells. Multiple pathways are involved in this action. The antitumor effects of viral infection on SGC-7901 and AGS cells were investigated. We measured endoplasmic reticulum stress and autophagy caused by the recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing the rabies virus glycoprotein (rL-RVG) and the NDV wild-type strain. The dose-response curves were analyzed using the MTT assay. The expression of RVG was detected by western blotting, RT-PCR and immunofluorescence analyses. Cell death and autophagy were observed using transmission electron microscopy, TUNEL and western blotting. Endoplasmic reticulum stress and the mitochondrial transmembrane potential were detected by western blotting and immunofluorescence, respectively. Immunofluorescence, western blot and RT-PCR analyses indicated that RVG gene and protein were expressed in SGC-7901 and AGS cells infected by rL-RVG. MTT and TUNEL analyses showed that the growth of SGC-7901 and AGS cells in the rL-RVG-infected group was significantly inhibited compared with the wild-type NDV-infected group (p<0.05). Western blot analysis indicated that rL-RVG and NDV induced increases in apoptosis, endoplasmic reticulum stress, and autophagy in the SGC-7901 and AGS cells. However, apoptosis and autophagy decreased in these cells after the application of the autophagy pathway inhibitor 3-MA or ATG-5-specific siRNA. Immunofluorescence analysis showed that the mitochondrial membrane potential collapsed. Taken together, these results indicate that the rL-RVG virus group is much more powerful compared with the NDV-infected group (p<0.05). rL-RVG and NDV are potent antitumor agents that induce autophagy.