Histamine regulates growth of malignant melanoma implants via H2 receptors in mice

The present study examined the effect of histamine H₂-receptor antagonists and exogenous histamine on growth of malignant melanoma implant in mice. Drugs were administered to B16BL6 malignant-melanoma-implanted syngeneic mice, and the tumor volume was measured throughout the experiments. Cell proliferation was assessed by MTT assay and mRNA expression was determined by RT-PCR. Both roxatidine and cimetidine significantly suppressed growth of B16BL6 implant compared with vehicle. On the other hand, systemically administered histamine significantly stimulated growth of B16BL6 implants. In addition, the histamine-stimulated B16BL6 implant growth was markedly suppressed by co-administration of cimetidine in a dose-dependent manner. H₂-receptor antagonists, however, failed to affect in vitro proliferation of B16BL6 cells. H₂-receptor mRNA was detected in B16BL6 implants but not in the cell line. These results indicated that both endogenous and exogenous histamine have ability to stimulate growth of malignant melanoma implants via H₂ receptors expressed in host cells.