Dendrobine inhibits anaplastic thyroid cancer progression by targeting the JAK-STAT3 pathway

Objective This study aimed to investigate the antitumor effects of dendrobine on ATC cells and its mechanism targeting the JAK-STAT3 pathway. Methods Human ATC cell lines (CAL-62 and 8505C) were treated with dendrobine (DEM). Detect cell viability, cell proliferation, cell apoptosis, cell migration and invasion. The expressions of E-cad, N-cad and Vim were detected by IF. JAK1, JAK2, STAT3 and their phosphorylated forms were quantified by WB. To probe pathway reversibility, cells were pretreated with IL-6 (20 ng/mL) or STAT3-siRNA before dendrobine exposure. In vivo , 6-week-old male BALB/c nude mice with 8505C xenografts were administered dendrobine (10 or 40 mg/kg/d) or saline for 21 d. Results Dendrobine reduced the viability of CAL-62 and 8505C cells, with 5 μM dendrobine achieving the most pronounced inhibition ( P < 0.001). Dendrobine treatment markedly suppressed cell proliferation ( P < 0.05) and colony formation ( P < 0.001), while increasing apoptosis ( P < 0.01). Dendrobine also inhibited migration and invasion ( P < 0.05), upregulated E-cad expression ( P < 0.001), downregulated N-cad and Vim expression ( P < 0.05), suggesting EMT inhibition. WB analysis confirmed that dendrobine suppressed phosphorylation of JAK1, JAK2, and STAT3 ( P < 0.05). However, IL-6 pretreatment reversed these effects by restoring p-JAK1, p-JAK2, and p-STAT3 levels ( P < 0.001) and partially rescuing cell proliferation and migration ( P < 0.001). Conversely, STAT3-siRNA transfection enhanced dendrobine’s inhibitory effects on proliferation, invasion, and migration ( P < 0.05) and further reduced JAK-STAT3 phosphorylation ( P < 0.05). In vivo , Dendrobine reduced tumor volume and weight ( P < 0.001), decreased IL-6 content in tumors ( P < 0.05), improved liver function indices by reducing AST, ALT and ALP activities ( P < 0.05), and exhibited no nephrotoxic effects. Conclusion Dendrobine exerts antitumor effects in ATC by targeting the JAK-STAT3 pathway, providing a promising therapeutic candidate.