銅螯合劑Ammonium tetrathiomolybdate(TTM)抑制銅死亡機制及研究應(yīng)用

Ammonium tetrathiomolybdate（TTM，AbMole, M54856）作為一種多功能無機鉬硫化合物，在基礎(chǔ)科研中展現(xiàn)出多重應(yīng)用。Ammonium tetrathiomolybdate能螯合銅離子[1]，干擾銅依賴性通路（如抑制ATP7B銅轉(zhuǎn)運蛋白表達(dá)、降低賴氨酰氧化酶活性及膠原交聯(lián)），并抑制銅死亡；Ammonium tetrathiomolybdate（TTM，CAS No.：15060-55-6）同時也能作為硫化氫供體，通過抑制線粒體氧化磷酸化、減少活性氧生成發(fā)揮調(diào)控作用[2]。此外，Ammonium tetrathiomolybdate（TTM，AbMole, M54856）還被證實可激活NRF2通路，抑制銅死亡相關(guān)效應(yīng)分子、并調(diào)控Akt/glucose攝取與乳酸代謝通路[1, 3]。
 

 
范例詳解
Front Oncol. 2025 Oct 10;15:1532772.
AbMoel的 Ammonium tetrathiomolybdate（TTM，AbMole, M54856）在本研究中作為銅死亡的抑制劑，通過對照實驗以驗證 FOXJ1 基因?qū)�宮頸癌細(xì)胞銅死亡的調(diào)控作用。研究結(jié)果表明，F(xiàn)OXJ1基因過表達(dá)顯著抑制宮頸癌細(xì)胞增殖、侵襲和遷移，并促進(jìn)銅死亡，而TTM通過螯合銅離子，抑制了銅死亡過程，從而逆轉(zhuǎn)了FOXJ1過表達(dá)的腫瘤抑制作用。  
參考文獻(xiàn)及鳴謝
[1] Ryumon, S.; Okui, T.; Kunisada, Y.; et al. Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. Oncology reports 2019, 42 (6), 2611-2621.
[2] Durham, T.; Zander, D.; Stomeo, N.; et al. Chemistry, pharmacology, and cellular uptake mechanisms of thiometallate sulfide donors. British journal of pharmacology 2020, 177 (4), 745-756.
[3] Navratilova, J.; Karasova, M.; Kohutkova Lanova, M.; et al. Selective elimination of neuroblastoma cells by synergistic effect of Akt kinase inhibitor and tetrathiomolybdate. Journal of cellular and molecular medicine 2017, 21 (9), 1859-1869.
[4] Sloan, C. Q.; Rodriguez, C. O., Jr. In vitro effects of doxorubicin and tetrathiomolybdate on canine hemangiosarcoma cells. American journal of veterinary research 2018, 79 (2), 219-225.
[5] Sachdeva, S.; Maret, W. Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate. Toxicology mechanisms and methods 2021, 31 (9), 690-698.
[6] Song, M.; Song, Z.; Barve, S.; et al. Tetrathiomolybdate protects against bile duct ligation-induced cholestatic liver injury and fibrosis. The Journal of pharmacology and experimental therapeutics 2008, 325 (2), 409-416.
[7] Derseh, H. B.; Perera, K. U. E.; Dewage, S. N. V.; et al. Tetrathiomolybdate Treatment Attenuates Bleomycin-Induced Angiogenesis and Lung Pathology in a Sheep Model of Pulmonary Fibrosis. Frontiers in pharmacology 2021, 12, 700902.
[8] Chan, N.; Willis, A.; Kornhauser, N.; et al. Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases. Clinical cancer research : an official journal of the American Association for Cancer Research 2017, 23 (3), 666-676.
[9] Cui, Y.; Liu, Z.; Zhang, L.; et al. Construction of a novel cuproptosis-related gene signature for predicting microenvironment, prognosis and therapeutic response in cervical cancer. Frontiers in oncology 2025, 15, 1532772.
 
細(xì)胞實驗參考
細(xì)胞系：AML cell cervical cancer cells
方法： The pENTER vector was used as a negative control. Ammonium tetrathiomolybdate (TTM) was purchased from AbMole (CAS No.:15060-55-6). Cells were treated with TTM at a final concentration of 40μM for 2 hours.
濃度：40μM
處理時間：2 h.
參考文獻(xiàn)：Front Oncol. 2025 Oct 10;15:1532772.  
* 上述方法來自公開文獻(xiàn)，僅供相同目的實驗參考。如實驗?zāi)康摹⒉牧�、方法不同，請參考其他文獻(xiàn)。
 
動物實驗參考
動物模型：C57BL/6N mice
配制：Distilled water
劑量：30 mg/kg
給藥處理：Oral gavage
參考文獻(xiàn)：Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H712-20.
*上述方法來自公開文獻(xiàn)，僅供相同目的實驗參考。如實驗?zāi)康摹⒉牧�、方法不同，請參考其他文獻(xiàn)。體內(nèi)實驗的工作液，建議現(xiàn)用現(xiàn)配，當(dāng)天使用；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過超聲和（或）加熱的方式助溶。
切勿一次性將產(chǎn)品全部溶解。
建議制定動物給藥及實驗方案時，盡量參考已發(fā)表的相關(guān)實驗文獻(xiàn)（溶劑種類及配比眾多，簡單地溶解目的化合物，并不能解決動物給藥依從性、體內(nèi)生物利用度、組織分布等相關(guān)問題，未必能保證目的化合物在動物體內(nèi)充分發(fā)揮生物學(xué)效用）。