TGF-β downregulation overcomes gemcitabine resistance in oral squamous cell carcinoma

OBJECTIVE: The aim of this study was to explore the mechanisms by which oral cancer acquires resistance to gemcitabine. METHODS: Oral squamous cell carcinoma (OSCC) cells were treated with gemcitabine upon infection or with a lentivirus harboring short hairpin RNA (shRNA) targeted to transforming gr...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer biomarkers : section A of Disease markers 2020-01, Vol.29 (2), p.179-187
Hauptverfasser: Xuan, Yun-Ze, Jin, Cheng-Ri, Yang, Kang-Juan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:OBJECTIVE: The aim of this study was to explore the mechanisms by which oral cancer acquires resistance to gemcitabine. METHODS: Oral squamous cell carcinoma (OSCC) cells were treated with gemcitabine upon infection or with a lentivirus harboring short hairpin RNA (shRNA) targeted to transforming growth factor-β (TGF-β). Then, Western blot, ELISA, migration assay, MTT assay, and animal experiments were used to explore the mechanism of resistance to gemcitabine treatment. RESULTS: After the treatment of non-transfected cells with gemcitabine, NF-κB and AKT activities were increased, which may have induced the OSCC resistance to gemcitabine. Then, we found that TGF-β downregulation effectively reduced NF-κB and AKT phosphorylation levels after the administration of gemcitabine and increased the OSCC sensitivity to gemcitabine, resulting in cell death and the blunting of OSCC resistance to gemcitabine. The EMT was also reduced by TGF-β downregulation combined with gemcitabine treatment. CONCLUSION: Cellular levels of TGF-β constitute an important factor in gemcitabine resistance and TGF-β silencing might represent a novel and potent strategy for overcoming OSCC resistance to gemcitabine.
ISSN:1574-0153
1875-8592
DOI:10.3233/CBM-201456