Abstract
Trichostatin A (TSA), a histone deacetylase inhibitor, is used as an anti-carcinogenic and radiosensitizing agent in various cancers. However, the role and mechanism underlying its radiosensitization of tongue squamous cell carcinoma (TSCC) remains unclear. Thus, in this study we aimed to confirm the promotion of miR‑375 expression by TSA, and to investigate the effects of TSA and miR‑375 in the radiosensitivity of TSCC cells. The results showed that TSA had significant radiosensitizing effects on TSCC cells and miR‑375 overexpression had effects similar to TSA in sensitizing these cells to radiotherapy. By contrast, miR‑375 knockdown attenuated apoptosis induced by radiation combined with TSA. Mechanistically, the histone acetylation status of the miR‑375 promoter region was increased by TSA, resulting in the upregulation of miR‑375, which led to a decline of PDK1 and phosphorylated AKT. Taken together, our data suggest that TSA increases the radiosensitization and apoptosis in TSCC cells at least partially via miR‑375, and TSA or miR‑375 in combination with radiotherapy may provide a valuable approach for the treatment of TSCC.
Highlights
Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well-known for its high rate of proliferation and nodal metastasis [1]
We demonstrated that Trichostatin A (TSA) sensitized TSCC cells to radiation
Our results demonstrated that TSA acted as a powerful radiosensitizer in TSCC cells by inhibiting cell growth and promoting apoptosis, consistent with previous studies in nonsmall cell lung cancer [7], cervical carcinoma [8], colon cancer [9], and erythroleukemic [10]
Summary
Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well-known for its high rate of proliferation and nodal metastasis [1]. TSCC is characterized as moderately resistant to radiotherapy and the outcome of radiotherapy is often not fully satisfactory due to. There have been several studies on the application of histone deacetylase (HDAC) inhibitors as anti-carcinogenic and radiosensitizing agents [4,5,6]. Trichostatin A (TSA), a pan-HDAC inhibitor, has been shown to enhance the radiosensitivity of a panel of human carcinoma cells [7,8,9,10,11,12,13]. Its effect on TSCC cell radioresistance and the underlying regulatory signal transduction pathways remain unclear
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