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Article type: Research Article
Authors: Xuan, Yun-Zea; 1 | Jin, Cheng-Ria; 1 | Yang, Kang-Juanb; *
Affiliations: [a] Department of Dentistry, Affiliated Hospital of Yanbian University, Yanji, Jilin, China | [b] Department of Cell Biology and Medical Genetics, Yanbian University College of Basic Medicine, Yanji, Jilin, China
Correspondence: [*] Corresponding author: Kang-Juan Yang, Department of Cell Biology and Medical Genetics, Yanbian University College of Basic Medicine, No. 977 of Gongyuan Street, Yanji, Jilin 133000, China. %****␣cbm-29-cbm201456_temp.tex␣Line␣100␣**** Tel.: +86 13620708625; E-mail: yangkj684107@163.com.
Note: [1] These authors contributed equally to this study.
Abstract: 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.
Keywords: OSCC, gemcitabine, resistance, TGF-β, lentivirus
DOI: 10.3233/CBM-201456
Journal: Cancer Biomarkers, vol. 29, no. 2, pp. 179-187, 2020
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