Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan.
Department of Radiology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan.
Int J Mol Sci. 2022 Aug 30;23(17):9872. doi: 10.3390/ijms23179872.
Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.
分化型甲状腺癌 (DTC) 患者通常预后良好，而晚期疾病患者的临床结局较差。本研究旨在探讨仑伐替尼联合碘（CTLI）治疗三种不同碘钠转运体（NIS）状态不同的 DTC 细胞系的抗肿瘤作用。放射性碘摄取研究显示，仑伐替尼治疗后 K1-NIS 细胞的放射性碘摄取明显增加，而 K1 和 FTC-133 细胞几乎没有摄取。然而，放射性碘治疗前给予仑伐替尼给药会降低体内成像研究中 K1-NIS 异种移植肿瘤的放射性碘摄取。CTLI 协同抑制集落形成和 DTC 细胞迁移，尤其是在 K1-NIS 细胞中。最后，碘治疗后给予仑伐替尼给药显著抑制 NIS 表达甲状腺癌异种移植模型的肿瘤生长。这些结果为联合治疗提供了重要的临床意义，即仑伐替尼应在碘治疗后给药，以最大限度地提高治疗效果。我们通过 CTLI 观察到的协同治疗效果表明，对于保留 NIS 功能的 RAI 阳性甲状腺癌，该联合治疗有效。这种潜在的联合治疗策略为晚期甲状腺癌提供了一种强大且耐受良好的新治疗策略。
