RESUMO
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.
RESUMO
Long non-coding RNA is an endogenous non-coding RNA that has currently been proved to be an important player in cancer cell biology. In the present study, we investigated the biological role of PHACTR2-AS1 in tongue squamous cell carcinoma (TSCC). PHACTR2-AS1 was preferentially localized in the cytoplasm, and was notably upregulated in TSCC tissues. High PHACTR2-AS1 was correlated with tumour differentiation, metastatic clinical features, relapse and shortened survival time. Depletion of PHACTR2-AS1 did not affect TSCC cell viability and colony formation ability, whereas substantially inhibited cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, PHACTR2-AS1 could sponge miR-137 to increase Snail expression, resulting in triggering epithelial-mesenchymal transition process, thereby promoting TSCC cell metastasis. Taken together, our data for the first time elucidate the metastasis-promoting role of PHACTR2-AS1 in TSCC, hinting a new therapeutic target for metastatic TSCC patients.