甲状腺未分化癌 (ATC) 是一种侵袭性恶性肿瘤，疾病特异性死亡率几乎为 100%，由于其对传统治疗的耐药性以及与阿霉素化疗等当前治疗方案相关的严重副作用，长期以来一直对肿瘤学构成巨大挑战。因此，迫切需要确定能够为 ATC 提供创新治疗策略的新型候选化合物。麦冬皂苷 D' (OPD') 是一种提取的三萜皂苷，但其在 ATC 中的作用尚未见报道。我们的数据表明 OPD' 有效抑制 ATC 细胞的增殖和转移，促进细胞周期停滞和细胞凋亡。值得注意的是，OPD' 在体外和体内均能阻碍 ATC 的生长和转移，显示出令人鼓舞的安全性。与正常组织相比，ATC 中 G 蛋白信号传导调节因子 4 (RGS4) 的表达显着上调，并且这种上调被 OPD 治疗所抑制。从机制上讲，我们阐明了转录因子 JUN 与 RGS4 启动子结合，驱动其反式激活。然而，OPD' 与 JUN 相互作用，减弱其转录活性，从而破坏 RGS4 过表达。总之，我们的研究表明OPD'与JUN结合，进而抑制RGS4的转录激活，从而引起ATC细胞的细胞周期停滞和凋亡。这些发现可能为开发用于 ATC 治疗的高质量候选化合物带来希望。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》

Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease-specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D' (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G-protein signalling 4 (RGS4) expression was significantly up-regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high-quality candidate compounds for treatment in ATC.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.