Yu Hongbo, Qu Ji, Gou Haixin, Zhou Ying
Department of Traditional Chinese Medicine Traumatology and Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.
Department of Vascular Medicine, Shanghai Traditional Chinese Medicine-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, P.R. China.
Exp Ther Med. 2024 Oct 15;28(6):456. doi: 10.3892/etm.2024.12746. eCollection 2024 Dec.
Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the endocrine system globally. Formononetin (FMNT), an isoflavonoid, exerts anti-tumorigenic effects and chromobox homolog 4 (CBX4) exerts tumor-promoting effect in specific types of tumors. Nevertheless, the predictive values and biological functions of FMNT and CBX4 in the pathological progress of PTC have not been fully understood till now. In the present study, the human PTC cell line TPC-1 was exposed to 0, 10, 30 and 100 µM FMNT for 24 h to elucidate the precise effects of FMNT on the biological behaviors of PTC cells. Moreover, FMNT-treated TPC-1 cells were transfected with oe-CBX4 to evaluate whether CBX4 was implicated in the anticarcinogenic effects of FMNT against PTC. It was demonstrated that FMNT treatment suppressed the proliferation, clone formation, migration, invasion, EMT, angiogenesis and stemness of PTC cells in a dose-dependent manner. Furthermore, it was verified that FMNT targeted CBX4 to downregulate its expression in a dose dependent manner. The suppressive effects of FMNT on the proliferation, clone formation, migration, invasion, EMT, angiogenesis and stemness of PTC cells were partially reversed by CBX4 overexpression. Upregulation of CBX4 abolished the tumor suppression effects of FMNT in the malignant progression of PTC. In conclusion, FMNT might act as a promising anti-tumorigenic agent in PTC, which depends on the downregulation of CBX4.
甲状腺乳头状癌（PTC）是全球内分泌系统最常见的恶性肿瘤。大豆苷元（FMNT）是一种异黄酮，具有抗肿瘤作用，而染色体框同源蛋白4（CBX4）在特定类型的肿瘤中发挥促肿瘤作用。然而，FMNT和CBX4在PTC病理进展中的预测价值和生物学功能至今尚未完全明确。在本研究中，将人PTC细胞系TPC-1分别暴露于0、10、30和100μM的FMNT中24小时，以阐明FMNT对PTC细胞生物学行为的精确影响。此外，用oe-CBX4转染经FMNT处理的TPC-1细胞，以评估CBX4是否参与FMNT对PTC的抗癌作用。结果表明，FMNT处理以剂量依赖性方式抑制PTC细胞的增殖、克隆形成、迁移、侵袭、上皮-间质转化（EMT）、血管生成和干性。此外，证实FMNT靶向CBX4并以剂量依赖性方式下调其表达。CBX4过表达部分逆转了FMNT对PTC细胞增殖、克隆形成、迁移、侵袭、EMT、血管生成和干性的抑制作用。CBX4的上调消除了FMNT在PTC恶性进展中的肿瘤抑制作用。总之，FMNT可能是一种有前景的PTC抗肿瘤药物，其作用依赖于对CBX4的下调。
