title: Effect of HMGB1 silencing on cell proliferation, invasion and apoptosis of MGC-803 gastric cancer cells.
abstract: High-mobility group box 1 (HMGB1) is a multifunctional protein with intranuclear and extracellular functions. Although HMGB1 is overexpressed in approximately 85% of gastric cancers, the role of HMGB1 in gastric cancer biology remains unclear. In this study, we investigate the effect of downregulation of HMGB1 on the biological behavior of gastric cancer cells. MGC-803 gastric cancer cells were transduced with HMGB1-specific RNAi lentiviral vectors. Real-time polymerase chain reaction and Western blot analysis of HMGB1 mRNA and protein, respectively, validated the silencing effects. HMGB1-specific silencing significantly decreased cell proliferation. The impact on proliferation was observed at the cell cycle level--the number of cells in the G0/G1 phase increased, whereas that in S and G2/M phases decreased. Cell cycle changes were accompanied by decreases in cyclin D1 expression. Furthermore, HMGB1 silencing sensitized cells to apoptosis that was induced by oxaliplatin and mediated by the caspase-3 pathway. Finally, silencing of HMGB1 expression significantly reduced cellular metastatic ability and MMP-9 expression in MGC-803 cells. In summary, HMGB1 not only plays an essential role in the proliferation and invasion of MGC-803 cells but also represents a potential target for the therapeutic intervention of gastric cancer.
authors.affiliation: Cancer Research Center, Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital & Institute, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Song
authors.forename: Wei-guo
authors.initials: WG
authors.lastname: Song
authors.forename: Zeng-jun
authors.initials: ZJ
authors.lastname: Li
authors.forename: Zhong-fa
authors.initials: ZF
authors.lastname: Xu
authors.forename: Xing-wu
authors.initials: XW
authors.lastname: Wang
authors.forename: Chuan-xi
authors.initials: CX
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D005822:Genetic Vectors; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019938:Cyclin D1; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9