The Impact of 125I Particle Implantation Therapy on Telomerase Activity and WNT5A/β-catenin Signaling Pathway in Thyroid Cancer Cells.

Radioactive iodine-125 (¹²⁵I) seed implantation is an increasingly important brachytherapy approach in cancer treatment. WNT5A is known to promote tumor cell proliferation and migration. This study aimed to elucidate the anticancer mechanisms of ¹²⁵I irradiation in thyroid cancer (TC) cells, with a particular focus on its effects on telomerase activity and the WNT5A/β-catenin signaling pathway. Telomerase activity in thyroid cancer (TC) cells was assessed using the telomeric repeat amplification protocol (TRAP) assay, and telomere length was determined by qPCR. The impact of ¹²⁵I irradiation on cell proliferation, invasion, and migration was measured by MTT, colony formation, Transwell, and wound healing assays. The underlying molecular pathways were investigated both in vitro and in a murine xenograft model. Compared with X-rays, ¹²⁵I irradiation produced markedly stronger cytotoxic effects, decreasing colony formation by ~ 45-60% and reducing telomerase activity by ~ 50%, while doubling apoptosis levels. It also impaired migration, lowering wound-healing closure by ~ 35-40% and reducing Transwell migration and invasion by 40-55%, accompanied by significant downregulation of WNT5A and β-catenin. Exogenous WNT5A partially restored β-catenin expression and improved migration by ~ 25%. In vivo, ¹²⁵I seed implantation reduced tumor volume by ~ 50% and final tumor weight by ~ 45% relative to X-ray treatment. Radioactive ¹²⁵I exerts its anticancer activity through a novel dual mechanism involving the downregulation of telomerase activity and the inactivation of WNT5A/β-catenin signaling. Our findings provide compelling preclinical evidence for the efficacy of ¹²⁵I particle brachytherapy in the treatment of patients with thyroid cancer.