Liu Yuan-Hao, Wu Li-Hsien, Fan Wen-Jun, Chiu Shih-Han, Chen Pei-Hsuan, Wang Chia C, Lee Che-Hsin
Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan.
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
J Cancer. 2024 Aug 13;15(16):5308-5317. doi: 10.7150/jca.96001. eCollection 2024.
Tellurium is a rare element, and ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) is the most bioactive molecule among several synthetic tellurium compounds. AS101 was found to be immunomodulatory and can modulate types of cytokines. However, the effect of AS101 on tumor metastasis remains unclear. Heparanase, an endo-glucuronidase, cleaves heparin sulfate side chains of proteoglycans on the cell surface, further leading to the degradation of the extracellular matrix. Heparanase also releases angiogenic factors in the extracellular matrix, is overexpressed in tumor cells, and promotes tumor metastasis and angiogenesis. In this study, we investigated the effect of AS101 in 4T1 and CT26 cells, especially heparanase. Heparanase expression was downregulated in 4T1 and CT26 cells after treatment with AS101 . The protein level involved in the protein kinase-B/mammalian target of rapamycin (AKT/mTOR) signaling pathway also declined. Cell migration assays revealed the inhibitory effect of AS101 on migration. The results of this study indicate that AS101 inhibits tumor migration by downregulating heparanase through the AKT/mTOR signaling pathway and has positive effects .
碲是一种稀有元素，三氯（二氧乙烯 - o,o'）碲酸铵（AS101）是几种合成碲化合物中生物活性最强的分子。研究发现AS101具有免疫调节作用，能够调节多种细胞因子。然而，AS101对肿瘤转移的影响仍不清楚。乙酰肝素酶是一种内切葡糖醛酸酶，可切割细胞表面蛋白聚糖的硫酸乙酰肝素侧链，进而导致细胞外基质降解。乙酰肝素酶还能释放细胞外基质中的血管生成因子，在肿瘤细胞中过度表达，并促进肿瘤转移和血管生成。在本研究中，我们研究了AS101对4T1和CT26细胞的影响，特别是对乙酰肝素酶的影响。用AS101处理后，4T1和CT26细胞中的乙酰肝素酶表达下调。蛋白激酶B/雷帕霉素哺乳动物靶标（AKT/mTOR）信号通路相关的蛋白水平也下降。细胞迁移实验揭示了AS101对迁移的抑制作用。本研究结果表明，AS101通过AKT/mTOR信号通路下调乙酰肝素酶来抑制肿瘤迁移，具有积极作用。
