Uptake in thyroid Tripterygium glycosides, enhances radioiodine cancer by promoting the expression and function of NIS

I monotherapy. This study demonstrates that TG can effectively restore NIS function and enhance RAI efficacy in thyroid cancer models with MAPK pathway hyperactivation and intrinsic NIS suppression. Its action is mediated through the dual regulation of NIS transcription and membrane localization following MAPK/ERK pathway inhibition. These findings provide preclinical proof-of-concept for TG as a potential redifferentiating agent targeting thyroid cancers with MAPK-driven intrinsic NIS suppression and establish a mechanistic rationale. Future studies in more advanced, dedifferentiated models (e.g., anaplastic thyroid cancer) are warranted to evaluate the broader applicability of this approach across the RAI-resistance spectrum.