Effects of clopidogrel bisulfate on B16-F10 cells and tumor development in a murine model of melanoma.

Abstract

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 (ADP) 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 72h at concentrations above 30 μM. In vivo, CB decreased the tumor nodule counts and LDH levels and increased platelet purine metabolism. Our results showed that CB has significant effects on melanoma progression.