Xi Chuang, Zhang Guoqiang, Sun Nan, Liu Mengyue, Ju Nianting, Shen Chentian, Song Hongjun, Luo Quanyong, Qiu Zhongling
Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
iScience. 2024 Apr 26;27(6):109829. doi: 10.1016/j.isci.2024.109829. eCollection 2024 Jun 21.
Homoharringtonine (HHT), an alkaloid isolated from , is an effective anti-leukemia agent and exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. Our findings demonstrated that HHT exhibited remarkable anti-TC activity that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells after HHT treatment. TIMP1 overexpression promoted TC progression and partially reversed the anti-TC effects of HHT, while TIMP1 downregulation inhibited TC progression and enhanced the anti-TC effects of HHT. Furthermore, TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, our study demonstrated that HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway.
高三尖杉酯碱（HHT）是从[具体来源未提及]中分离出的一种生物碱，是一种有效的抗白血病药物，对多种实体瘤均有抑制作用。然而，HHT治疗对甲状腺癌（TC）的影响尚不清楚。我们的研究结果表明，HHT具有显著的抗TC活性，包括抑制细胞增殖、侵袭和迁移，以及诱导细胞凋亡。蛋白质组学分析显示，HHT处理后，TC细胞中金属蛋白酶组织抑制剂1（TIMP1）的表达下调。TIMP1过表达促进TC进展，并部分逆转HHT的抗TC作用，而TIMP1下调则抑制TC进展并增强HHT的抗TC作用。此外，TIMP1重新表达减弱了TIMP1敲低诱导的HHT抗TC作用的增强。机制上，HHT通过下调TIMP1表达，进而使FAK/PI3K/AKT信号通路失活，发挥抗TC作用。综上所述，我们的研究表明，HHT可通过抑制TIMP1/FAK/PI3K/AKT信号通路来抑制TC进展。
