乳酸脱氢酶
黑色素瘤
血小板
P2Y12
肿瘤微环境
化学
癌症研究
嘌呤能受体
细胞生长
药理学
活力测定
转移
癌症
腺苷
内科学
生物
医学
细胞
生物化学
酶
血小板聚集
作者
Matheus Henrique Jantsch,Pedro H. Doleski,Altevir Rossato Viana,Jean Lucas Gutknecht da Silva,Daniela F. Passos,Fernanda Licker Cabral,Alessandra Guedes Manzoni,Renan da Silva Ebone,Ana Bárbara Uchoa Soares,Cínthia Melazzo de Andrade,Maria Rosa Chitolina Schetinger,Daniela Bitencourt Rosa Leal
标识
DOI:10.1139/bcb-2022-0249
摘要
Metastatic melanoma is a very aggressive skin cancer. Platelets are constituents of the tumor microenvironment and, when activated, contribute to cancer progression, especially metastasis and inflammation. P2Y12 is an adenosine diphosphate receptor that triggers platelet activation. Inhibition of P2Y12 by clopidogrel bisulfate (CB) decreases platelet activation, which is also controlled by the extracellular concentration and the metabolism of purines by purinergic enzymes. We evaluated the effects of CB on the viability and proliferation of cultured B16-F10 cells. We also used a metastatic melanoma model with C57BL-6 mice to evaluate cancer development and purine metabolism modulation in platelets. B16-F10 cells were administered intraperitoneally to the mice. Two days later, the animals underwent a 12-day treatment with CB (30 mg/kg by gavage). We have found that CB reduced cell viability and proliferation in B16-F10 culture in 72 h at concentrations above 30 µm. In vivo, CB decreased tumor nodule counts and lactate dehydrogenase levels and increased platelet purine metabolism. Our results showed that CB has significant effects on melanoma progression.
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