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.

中文翻译：

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硫酸氢氯吡格雷对黑色素瘤小鼠模型中 B16-F10 细胞和肿瘤发展的影响。

转移性黑色素瘤是一种非常侵袭性的皮肤癌。血小板是肿瘤微环境的组成部分，当被激活时，会促进癌症进展，特别是转移和炎症。P2Y12 是一种二磷酸腺苷受体，可触发血小板活化。氯吡格雷硫酸氢盐 (CB) 对 P2Y12 的抑制会降低血小板活化，这也受到细胞外浓度和嘌呤能酶的嘌呤代谢的控制。我们评估了 CB 对培养的 B16-F10 细胞活力和增殖的影响。我们还使用 C57BL-6 小鼠的转移性黑色素瘤模型来评估癌症的发展和血小板中嘌呤代谢的调节。将B16-F10细胞腹膜内给予小鼠。两天后，动物接受为期 12 天的 CB 治疗（灌胃 30 mg/kg）。我们发现，浓度高于 30 µm 的 CB 在 72 小时内会降低 B16-F10 培养物中的细胞活力和增殖。在体内，CB 减少肿瘤结节计数和乳酸脱氢酶水平，并增加血小板嘌呤代谢。我们的结果表明，CB 对黑色素瘤的进展有显着影响。