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

Zhongtao Zhang; Lin Hu; Zhigang Bai; Xuemei Ma; Nan Bai

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자료유형: 학술저널

저자정보: Zhongtao Zhang Lin Hu Zhigang Bai Xuemei Ma Nan Bai

저널정보: 대한위암학회 Journal of Gastric Cancer Journal of Gastric Cancer 제20권 제1호

발행연도: 2020.1

수록면: 95 - 105 (11page)

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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.

참고문헌 (24)

참고문헌 신청

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