title: Autophagy is involved in recombinant Newcastle disease virus (rL-RVG)-induced cell death of stomach adenocarcinoma cells in vitro.
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.
authors.affiliation: Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Bu
authors.affiliation: Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Mu-Bing
authors.initials: MB
authors.lastname: Wang
authors.affiliation: Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Ying-Hai
authors.initials: YH
authors.lastname: Zhao
authors.affiliation: Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059865:Endoplasmic Reticulum Stress; D005822:Genetic Vectors / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009522:Newcastle disease virus / Q000235:genetics* / Q000502:physiology; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology; D011820:Rabies virus / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000628:therapy*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D011994:Recombinant Proteins; D014764:Viral Proteins