title: Proteomic analyses of gastric cancer cells treated with vesicular stomatitis virus matrix protein.
abstract: Gastric cancer constitutes the second leading cause of mortality worldwide and the fourth most common cancer. While chemotherapy remains the primary treatment for both resectable and advanced gastric cancer, most gastric cancers are naturally resistant to anticancer drugs, rendering new therapeutic avenues in dire need. Vesicular stomatitis virus (VSV) was proved to preferentially replicate in many types of tumor cells and eventually induce apoptosis of host cells. The vesicular stomatitis virus matrix protein (MP) plays a major role in its effects. This study proved that expression of MP could effectively inhibit proliferation and induce cell death in gastric carcinoma MKN28 cells. Furthermore, we utilized a proteomics strategy to characterize proteome-wide alterations between MP-treated MKN28 lines and their untreated counterparts. A total of 97 spots were positively identified as differentially expressed, and of these 62 proteins were up-regulated, whereas 35 proteins were down-regulated. Functional analysis unraveled three significantly modified gene product subgroups: glycolytic enzymes, reactive oxygen species-associated proteins and the proteins regulating RNA transport and maturation. Expression of three altered proteins was further validated by semi-quantitative RT-PCR or/and western blotting. Furthermore, we demonstrated that MP expression could induce rapid intracellular ROS accumulation in MKN28 cells. These results provide evidence for the anti-cancer potential of MP, and a novel MP-mediated apoptotic signaling pathway is proposed. Our findings are considered a significant step toward a better understanding the mechanism of MP-induced anti-cancer effect.
authors.affiliation: The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Zeng
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhou
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Lei
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.forename: Canhua
authors.initials: C
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D010957:Plasmids / Q000235:genetics; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D017382:Reactive Oxygen Species; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D053719:Tandem Mass Spectrometry; D014162:Transfection; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C094460:M protein, Vesicular stomatitis virus; D020543:Proteome; D017382:Reactive Oxygen Species; D014763:Viral Matrix Proteins