Mometasone Furoate Inhibits the Progression of Head and Neck Squamous Cell Carcinoma via Regulating Protein Tyrosine Phosphatase Non-Receptor Type 11

Abstract

Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and neck squamous cell carcinoma (HNSCC) is still unclear. This study aimed to evaluate the inhibitory effect of MF against HNSCC and investigate its underlying mechanisms. Cell viability, colony formation, cell cycle and cell apoptosis were analyzed to explore the effect of MF on HNSCC cells. A xenograft study model was used to investigate the effect of MF on HNSCC in vivo. The core targets of MF for HNSCC were identified using network pharmacology analysis, TCGA database analysis and real-time PCR. Molecular docking was performed to determine the binding energy. Protein tyrosine phosphatase non-receptor type 11 (PTPN11)-overexpressing cells were constructed, and then, the cell viability and the expression levels of proliferation- and apoptosis-related proteins were detected after treatment with MF to explore the role of PTPN11 in the inhibitory effect of MF against HNSCC. After cells were treated with MF, cell viability and the number of colonies were decreased, the cell cycle was arrested and cell apoptosis was increased. The xenograft study results showed that MF could inhibit cell proliferation via promoting cell apoptosis in vivo. PTPN11 was shown to be the core target of MF against HNSCC via network pharmacology analysis, TCGA database analysis and real-time PCR. The molecular docking results revealed that PTPN11 exhibited the strongest ability to bind to MF. Finally, MF could attenuate the effects of increased cell viability and decreased cell apoptosis caused by PTPN11 overexpression, suggesting that MF can inhibit the progression of HNSCC by regulating PTPN11. MF targeted PTPN11, promoting cell cycle arrest and cell apoptosis, and consequently exerting effective anti-tumor activity.

Editorial of Special Issue “Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches”

“…Therefore, non-invasive biomarkers such as tumor oxygenation and signals from autofluorescence imaging, intensity signals from optical coherence tomography, and ultrasound wave signals from surface tumor tissues have been shown to provide accurate predictions for early detection and prognosis assessments in OSCC [30]. To overcome these challenges, this Special Issue has accepted a few publications that highlighted the potential biomarkers that can be used for diagnostic and therapeutic purposes [31][32][33][34][35][36][37][38][39][40]. The diagnostic section can be divided into biomarkers for OSCC and prognosis.…”

“…This Special Issue also published a comprehensive review that provides an update on recent studies using preclinical models of HNSCC to investigate the role of natural products as therapeutic or chemo preventive agents to improve patient clinical outcomes [39]. In addition to the potential of natural products as therapeutic agents for HNSCC, this Special Issue also published an original article highlighting the role of mometasone furoate (MF) as a potential therapeutic agent targeting PTPN11, which halts tumorigenesis in vitro and impairs tumor growth in vivo using a preclinical model of HNSCC [31]. For the diagnostic approach that focuses on the early detection in OSCC, Surendran et al [37] demonstrated the gradual increments in the infiltration of Tregs (CD4, CD25, FOXP3), exhausted CD8 T cells (CD8 and PD-1) in the immune microenvironment, and the expression of PD-L1 in epithelial cells in the oral carcinogenesis mechanism, from normal epithelium to dysplasia and eventually to invasive SCC.…”