Regardless of recent progress,
melanoma is very difficult to treat, mainly due to the drug resistance modulated by
tumor cells as well as by the tumor microenvironment (TME). Among the immune cells recruited at the
tumor site, tumor associated macrophages (TAMs) are the most abundant, promoting important tumorigenic processes: angiogenesis,
inflammation and invasiveness. Furthermore, it has been shown that TAMs are involved in mediating the drug resistance of
melanoma cells. Thus, in the present study, we used liposomal formulation of
prednisolone disodium
phosphate (LCL-PLP) to inhibit the protumor function of TAMs with the aim to sensitize the
melanoma cells to the cytotoxic
drug doxorubicin (DOX) to which human
melanoma has intrinsic resistance. Consequently, we evaluated the in vivo effects of the concomitant administration of LCL-PLP and liposomal formulation of DOX (LCL-DOX) on B16.F10
melanoma growth and on the production of key molecular markers for
tumor development. Our results demonstrated that the concomitant administration of LCL-PLP and LCL-DOX induced a strong inhibition of
tumor growth, primarily by inhibiting TAMs-mediated angiogenesis as well as the
tumor production of MMP-2 and
AP-1. Moreover, our data suggested that the combined
therapy also affected TME as the number of infiltrated macrophages in
melanoma microenvironment was reduced significantly.