Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells

Fang, Liang; Gao, Li; Xie, Lei; Xiao, Guizhou

doi:10.7150/jca.26136

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J Cancer 2018; 9(19):3479-3488. doi:10.7150/jca.26136 This issue Cite

Research Paper

Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells

Liang Fang^✉, Li Gao, Lei Xie, Guizhou Xiao

Department of head and neck surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, P.R. China

Citation:

Fang L, Gao L, Xie L, Xiao G. Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells. J Cancer 2018; 9(19):3479-3488. doi:10.7150/jca.26136. https://www.jcancer.org/v09p3479.htm

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Abstract

Background: Epithelial-mesenchymal transition (EMT) is considered to be vital during chemotherapy resistance in oral squamous cell carcinoma (OSCC). Recently, eukaryotic initiation factor 5A-2 (eIF5A-2), a potential oncogene, has been reported to be involved in chemotherapy resistance in human cancers.

Materials and Methods: N1-guanyl-1,7-diaminoheptane (GC7, a novel eIF5A-2 inhibitor) or siRNA on responses to doxorubicin were examined in OSCC cells. Cytotoxicity and protein expression were evaluated by CCK-8 and EdU incorporation assay and western blotting. Tca8113 cells were used for establishment and treatment of tumor xenografts in vivo.

Results: Low concentration of GC7 (5μΜ) significantly enhanced doxorubicin cytotoxicity in both epithelial phenotype OSCC cells (Cal27) and mesenchymal phenotype OSCC cells (HN30 and Tca8113). EMT process promoted by doxorubicin in Cal27 cells could be reversed by GC7. Additionally, GC7 induced mesenchymal-epithelial transition (MET) in HN30 and Tca8113 cells. Silencing of eIF5A-2 by specific siRNA exhibited the similar effects. The synergistic cytotoxicity of doxorubicin/GC7 combination was not induced in Twist-1, an EMT driving factor, silenced Cal27, HN30, and Tca8113 cells. GC7 also synergized doxorubicin to inhibit tumor growth in vivo treatment.

Conclusions: Our study strongly proved that combined treatment with GC7 may boost the therapeutic effect of doxorubicin in OSCC by inhibiting the EMT.

Keywords: Eukaryotic initiation factor 5A-2 (eIF5A-2), N1-guanyl-1, 7-diaminoheptane (GC7), Oral squamous cell carcinoma (OSCC), Epithelial-mesenchymal transition (EMT), doxorubicin, chemo-resistance

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APA

Fang, L., Gao, L., Xie, L., Xiao, G. (2018). Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells. Journal of Cancer, 9(19), 3479-3488. https://doi.org/10.7150/jca.26136.

ACS

Fang, L.; Gao, L.; Xie, L.; Xiao, G. Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells. J. Cancer 2018, 9 (19), 3479-3488. DOI: 10.7150/jca.26136.

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CSE

Fang L, Gao L, Xie L, Xiao G. 2018. Eukaryotic translation initiation factor 5A-2 involves in doxorubicin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells. J Cancer. 9(19):3479-3488.

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