Histamine and clozapine treatments inhibit tumor growth and increase median survival in human melanoma xenograft model.

N MASSARI; VA MEDINA; M CROCI; L SAMBUCO; D MARTINEL LAMAS; RM BERGOC; ES RIVERA

Congreso; European Histamine Research Society, XLI Annual Meeting; 2012

Melanoma accounts for less than 5% of skin cancer cases but causes a large majority of skin cancer deaths. The expression of all histamine receptors (HR) subtypes were demonstrated in human melanoma cell lines, and the activation of the H4R in WM35 primary and M1/15 highly metastatic human melanoma cells inhibits proliferation and migration, and induces differentiation and senescence. The aim of this work was to evaluate the in vivo antitumor potential of histamine (HA) and clozapine (CLZ, H4R agonist) on human melanoma. An experimental model was developed by subcutaneous (sc) injection of M1/15 cells into the right flank of athymic nude mice. Animals were separated into three groups: control, HA (1mg.kg-1, sc) and CLZ (1mg.kg-1, sc). Tumors were excised and the expression levels of H4R, HA and histidine decarboxilase (HDC) were studied by immunohistochemistry. Cell growth was assessed by PCNA expression and by mitotic index (MI). Finally, vascularization was determined by Massons trichromic staining, and invasion markers by metalloproteases (MMP-2 and MMP-9) expression levels. Mice receiving HA or CLZ showed a median survival increase (61 d) vs. control group (40 d) (treated with saline solution) (p