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http://dx.doi.org/10.5230/jgc.2020.20.e9

The Influence of Bcl-3 Expression on Cell Migration and Chemosensitivity of Gastric Cancer Cells via Regulating Hypoxia-Induced Protective Autophagy  

Hu, Lin (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases)
Bai, Zhigang (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases)
Ma, Xuemei (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases)
Bai, Nan (Department of General Surgery, Beijing Jishuitan Hospital, The 4th Medical College of Peking University)
Zhang, Zhongtao (Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases)
Publication Information
Journal of Gastric Cancer / v.20, no.1, 2020 , pp. 95-105 More about this Journal
Abstract
Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.
Keywords
Bcl-3; $HIF-1{\alpha}$; Autophagy; Migration; Chemosensitivity;
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