The poor prognosis of locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC) is primarily mediated by the functional properties of cancer stem cells (CSCs) and resistance to chemoradiotherapy. We investigated whether the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF) can enhance the sensitivity of therapy. Cell viability was assessed by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and apoptosis assays, and the cell cycle and reactive oxygen species (ROS) levels were evaluated by fluorescence-activated cell sorting (FACS). The radio-sensitizing effect was measured by a colony formation assay. The synergistic effects were calculated by combination index (CI) analyses. The DSF and DSF/Cu²⁺ inhibited the cell proliferation (inhibitory concentration 50 (IC₅₀) of DSF and DSF/Cu²⁺ were 13.96 μM and 0.24 μM). DSF and cisplatin displayed a synergistic effect (CI values were <1). DSF or DSF/Cu²⁺ abolished the cisplatin-induced G2/M arrest (from 52.9% to 40.7% and 41.1%), and combining irradiation (IR) with DSF or DSF/Cu²⁺ reduced the colony formation and attenuated the G2/M arrest (from 53.6% to 40.2% and 41.9%). The combination of cisplatin, DSF or DSF/Cu²⁺, and IR enhanced the radio-chemo sensitivity by inducing apoptosis (42.04% and 32.21%) and ROS activity (46.3% and 37.4%). DSF and DSF/Cu²⁺ enhanced the sensitivity of HNSCC to cisplatin and IR. Confirming the initial data from patient-derived tumor xenograft (PDX) supported a strong rationale to repurpose DSF as a radio-chemosensitizer and to assess its therapeutic potential in a clinical setting.

Nasal mucosal epithelial hyperplasia can cause nasal hyperplastic diseases, more studies have confirmed that different subtypes of HPV infection play a significant role in nasal proliferative diseases, especially nasal inverted papilloma (NIP). This study aims to elucidate the role and mechanism of the HPV11 subtype in regulating nasal epithelial hyperplasia. In our previous study, the expression of HPV infection in NIP was analyzed by Flow-through hybridization and gene chip (HybridMax), with the highest expression rate observed for the HPV11 subtype. Therefore, we aimed to overexpress HPV11E6/E7 in nasal mucosal epithelial cells (HNEpC) to verify the regulatory role and mechanism of HPV11 in nasal epithelial hyperplasia at the cellular level. In this manuscript, we constructed a lentiviral vector overexpressing HPV11E6/E7 and transfected it into HNEpC. We used HNEpC as the control group and HPV11E6/E7-overexpressing cells as the experimental group. Cell proliferation was assessed using CCK-8, EdU, and colony formation assays. Cell migration ability was evaluated by wound healing and Transwell assays. Protein expression levels related to apoptosis, epithelial–mesenchymal transition (EMT), and the JAK2/STAT3 pathway were analyzed by western blot. The results showed that overexpression of HPV11E6/E7 significantly increased the proliferation and migration of nasal epithelial cells, promoted the progression of EMT, and inhibited cell apoptosis. Further verification showed that the overexpression of HPV11E6/E7 significantly promoted the activation of the JAK2/STAT3 signaling pathway. In summary, we found that low-risk subtype HPV11 promotes nasal mucosal epithelial hyperplasia and malignant progression by increasing activation of the JAK2/STAT3 pathway. The JAK2/STAT3 pathway has been prioritized due to its established role in promoting cell proliferation and EMT in HPV-related diseases.