期刊
BIOMEDICINES
卷 6, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines6020062
关键词
deubiquitinylases; NF-kappa B signaling; apoptotic cell death; gastric carcinoma; therapeutic targets; chemoresistance; ubiquitin-specific proteases
资金
- Ministery of Economy, Science and Digitalisation (Forderung von Wissenschaft und Forschung in Sachsen-Anhalt aus Mitteln der Europaischen Struktur- und Investitionsfonds in der Forderperiode [ZS/2016/04/78155]
- Medical Faculty of the Otto von Guericke University
Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of gastric cancer patients comprises a gastrectomy and perioperative or adjuvant chemotherapy. However, resistance of gastric cancer cells to these agents is widespread; thus, improved chemotherapeutic approaches are required. Nuclear factor kappa B (NF-kappa B) transcription factors are associated with anti-apoptosis, carcinogenesis, and chemoresistance, and thus, constitute attractive targets for therapeutic intervention. In immunoblots, we show that ubiquitin specific protease 47 (USP47) promotes beta-transducin repeat-containing protein (beta TrCP) stability and phosphorylation of RelA. Furthermore, after knockdown of USP47 by RNA interference, we analyzed in gastric cancer cell lines metabolic activity/viability in an MTT assay, and apoptotic cell death by Annexin V staining and poly(ADP-Ribose) polymerase (PARP)-1, caspase 3, and caspase 8 cleavage, respectively. We found that USP47 contributes to cell viability and chemoresistance in NCI-N87 gastric carcinoma cells treated with etoposide and camptothecin. Inhibition of USP47 might be a suitable strategy to downregulate NF-kappa B activity, and to overcome chemoresistance in gastric cancer.
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