Lee Jie-Jen, Hsu Yi-Chiung, Li Ying-Syuan, Cheng Shih-Ping
Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei 104215, Taiwan.
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City 320317, Taiwan.
Int J Endocrinol. 2021 May 7;2021:5583491. doi: 10.1155/2021/5583491. eCollection 2021.
Accumulating evidence suggests that galectin-3 is a histologic marker of thyroid cancer. However, the pharmacological lectin-based approach has not been well studied. In the present study, we aimed to investigate the therapeutic potential of novel galectin-3 inhibitors by treating thyroid cancer cells with different concentrations of GB1107 or TD139. At high doses, TD139, but not GB1107, reduced cell viability and clonogenicity of thyroid cancer cells. TD139 induced apoptosis of thyroid cancer cells, as evident by an increase in the percentage of sub-G1 cells on cell cycle analysis, caspase-3 activation, and PARP1 cleavage. Either GB1107 or TD139 significantly inhibited cell coherence and counteracted anoikis resistance. Both inhibitors decreased migratory and invasive abilities in a dose-dependent manner. Furthermore, GB1107 and TD139 treatment attenuated AKT phosphorylation and decreased the expression of -catenin and MMP2. In conclusion, these novel galectin-3 inhibitors suppressed the anoikis resistance, motility, and invasive capacity of thyroid cancer cells at least partly through the AKT/-catenin pathway. Galectin-3 inhibitors are potentially suitable for preclinical evaluation of treatment and/or prevention of metastatic spread in thyroid cancer.
越来越多的证据表明，半乳糖凝集素-3是甲状腺癌的组织学标志物。然而，基于药理学凝集素的方法尚未得到充分研究。在本研究中，我们旨在通过用不同浓度的GB1107或TD139处理甲状腺癌细胞来研究新型半乳糖凝集素-3抑制剂的治疗潜力。高剂量时，TD139而非GB1107降低了甲状腺癌细胞的细胞活力和克隆形成能力。TD139诱导甲状腺癌细胞凋亡，细胞周期分析中G1期前细胞百分比增加、半胱天冬酶-3激活和PARP1裂解均证明了这一点。GB1107或TD139均显著抑制细胞黏附并抵消失巢凋亡抗性。两种抑制剂均以剂量依赖性方式降低迁移和侵袭能力。此外，GB1107和TD139处理减弱了AKT磷酸化并降低了β-连环蛋白和MMP2的表达。总之，这些新型半乳糖凝集素-3抑制剂至少部分通过AKT/β-连环蛋白途径抑制甲状腺癌细胞的失巢凋亡抗性、运动性和侵袭能力。半乳糖凝集素-3抑制剂可能适合于甲状腺癌转移扩散治疗和/或预防的临床前评估。
