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Selinexor assists vorinostat in inhibiting HDAC activity via promoting the accumulation of maspin in the nucleus of oral tongue squamous cell carcinoma cells

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Abstract

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer with a low overall survival rate, necessitating effective treatments. This study reports the anti-OTSCC effect of vorinostat and selinexor. OTSCC cell lines SCC-4 and SCC-25 were cultured to determine the effects of vorinostat and/or selinexor on cell survival, invasion, migration, and apoptosis. The transplanted tumor model of SCC-25 in nude mice was established to observe the therapeutic effects of vorinostat and/or selinexor. Western blotting was used to determine protein expressions in tumor cells. The results showed that histone deacetylase 1 (HDAC1) and exportin 1 (XPO1) were highly expressed, while nuclear maspin was expressed at a low rate in SCC-4 and SCC-25 compared to the normal tongue tissue. In vitro, both vorinostat and selinexor effectively inhibited cell viability, invasion, and migration, promoted cell apoptosis, down-regulated HDAC1, Matrix Metalloproteinase 2 (MMP2), and B cell leukemia/lymphoma 2 (Bcl-2), and up-regulated nuclear maspin and cleaved caspase 3. In vivo, both vorinostat and selinexor inhibited the growth of SCC-25-bearing tumors, down-regulated the expression of Ki67, HDAC1, MMP2, and Bcl-2, and promoted the expression of nuclear maspin and cleaved caspase 3. The combination of these two drugs exhibited synergistic effects both in vivo and in vitro. Our evidence shows that vorinostat combined with selinexor is an effective treatment for OTSCC. The mechanism may be that selinexor promotes the accumulation of maspin in the nucleus, an endogenous HDAC1 inhibitory protein to inhibit the HDAC1 activity of vorinostat and exert a synergistic anti-OTSCC effect.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Head and Neck Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, 519 East Beijing Road, Nanchang, 330029, Jiangxi, China

    Fenqian Yuan, Jingkang Yong, Xueming Liu & Yifeng Wang

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  1. Fenqian Yuan
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  2. Jingkang Yong
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  3. Xueming Liu
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  4. Yifeng Wang
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Contributions

FY: Conceptualization, Visualization, Data curation, Writing—original draft, Formal analysis. JY: Project Administration, Investigation, Methodology, Funding acquisition, Writing—review & editing. Xl: Visualization, Methodology, Data curation. YW: Formal analysis, Project Supervision. All authors reviewed the manuscript.

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Correspondence to Yifeng Wang.

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Yuan, F., Yong, J., Liu, X. et al. Selinexor assists vorinostat in inhibiting HDAC activity via promoting the accumulation of maspin in the nucleus of oral tongue squamous cell carcinoma cells. Cytotechnology 75, 1–16 (2023). https://doi.org/10.1007/s10616-022-00555-x

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