Objective We examined the levels of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in head and neck squamous cell carcinoma (HNSCC) and their influence on chemotherapy sensitization.

Methods Sixty patients with HNSCC who were treated at Tianjin Medical University Cancer Institute & Hospital, between January 2018 and December 2022, were included in the study. Levels of expressed JAK2, p-STAT3^Y705, c-Myc, and Ki-67 in HNSCC tissues were evaluated using immunohistochemical staining, and correlation analysis was performed. The viability of UM-SCC1 cells treated with fedratinib, a JAK2 inhibitor, combined with cisplatin (DDP) and paclitaxel (PTX) was determined using the CCK8 assay. Western blot was performed to detect p-STAT3^Y705 expression in tumor tissues and HNSCC cell lines. SCC15 and UM-SCC1 cell lines stably transfected with JAK2 or STAT3 vectors were constructed and verified. Cell activity and cell proliferation capacity were measured to evaluate the detrimental impact of STAT3 overexpression on chemotherapy with fedratinib using Western blot, CCK8, and plate cloning assays.

Results JAK2 expression in HNSCC positively correlated with p-STAT3^Y705 (r=0.43, P<0.000 1) and c-Myc (r=0.48, P<0.01) expression. High p-STAT3^Y705 expression positively correlated with AJCC stage (P<0.0001) and Ki-67 expression (P<0.05). High STAT3 and p-STAT3 levels were associated with poor prognosis in patients with HNSCC. In vitro, the JAK2 inhibitor fedratinib inhibited HNSCC cell proliferation and enhanced tumor cell sensitivity to DDP and PTX. JAK2 activation promotes STAT3 phosphorylation, and STAT3 overexpression reverses the effects of fedratinib on HNSCC sensitivity to chemotherapy.

Conclusions JAK2/STAT3 signaling is elevated in patients with HNSCC. Targeting the JAK2/STAT3 pathway is a potential method for increasing the sensitivity of HNSCC to chemotherapy.