Knockdown of High Mobility Group-Box 3 (HMGB3) Expression Inhibits Proliferation, Reduces Migration, and Affects Chemosensitivity in Gastric Cancer Cells
Shengnan Guo, Yuanyuan Wang, Yu Gao, Yinxu Zhang, Mingzi Chen, Minghao Xu, Lu Hu, Yu Jing, Fangyu Jing, Chen Li, Qingjun Wang, Zhitu Zhu
(Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland))
Med Sci Monit 2016; 22:3951-3960
High mobility group-box 3 (HMGB3) has been shown to affect tumor initiation and progression. This research aimed to investigate the role of HMGB3 in gastric cancer (GC) cell proliferation, migration, invasion, chemoresistance, and its potential molecular mechanisms.
MATERIAL AND METHODS: GC MGC803 and BGC823 cells were transfected with siRNA targeting the HMGB3 gene. The expressions of HMGB3 protein in MGC803 and BGC823 cells after transfection were detected by Western blot assays. We detected cell proliferation and cell cycle by MTT and flow cytometry assay. Cell migration and invasion were determined by wound scratch and transwell assay. MGC803 and BGC823 cells were treated with various concentrations of oxaliplatin, cisplatin, and paclitaxel. After 24 hours of drug exposure, we performed MTT assays to investigate chemoresistance in both groups. Western blot assays were used to detect related proteins expression.
RESULTS: Silencing of HMGB3 inhibited cell proliferation and induced G0/G1 phase arrest of GC cells partly via modulating p53 and p21 pathways, and downregulating Bcl-2/Bax ratio. RNA interference of HMGB3 inhibited cell invasion and migration by downregulating MMP2 and MMP9. Silencing of HMGB3 enhanced sensitive to cisplatin and paclitaxel, and reduced sensitive to oxaliplatin.
CONCLUSIONS: These findings suggest the importance of HMGB3 in the regulation of growth, migration, and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies.
Keywords: Cell Migration Inhibition, Cell Proliferation, Drug Resistance, HMGB3 Protein, RNA, Small Interfering, Stomach Neoplasms