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- Title
TARGETING MELANOMA MICROENVIRONMENT WITH LIPOSOMAL PREDNISOLONE IMPROVED THE THERAPEUTIC OUTCOME OF LIPOSOMAL DOXORUBICIN.
- Authors
LICARETE, EMILIA; DROTAR, DENISE-MINERVA; STEJEREAN, IOANA; PATRAS, LAURA; RAUCA, VALENTIN-FLORIAN; LUPUT, LAVINIA; SESARMAN, ALINA; BANCIU, MANUELA
- Abstract
Recent research in the melanoma field has contributed to a better understanding of the molecular mechanisms responsible for tumor growth and metastasis as well as drug resistance and led to approval of several novel therapies such as immune check point inhibitors and targeted therapy with Braf and Mek inhibitors. Although a survival benefit was obtained after the use of these novel biological agents, the resistance to treatment remains a major problem. To overcome this limitation, combination therapies have been developed but, despite to clinical efficacy, they are associated with serious adverse effects and are restricted to molecularly defined subsets of patients. In many types of cancer, including melanoma, TAMs are polarized to M2 phenotype supporting tumor growth, inflammation, angiogenesis, immunosuppression, and metastasis. Additionally, TAMs were associated with a lower efficacy of several cytotoxic drugs. In this context and based on our reported results, the aim of the present study was to develop a combination therapy based on liposomal prednisolone (LCL-PLP) as a tumor microenvironment modulator and liposomal doxorubicin (LCL-DOX) as a cytotoxic drug for melanoma cells. To this aim, 10 mg/kg of PLP and 5 mg/kg of DOX in long circulating liposomes (LCL) were administered simultaneously as well as separately to B16F10 tumor bearing mice. Our result demonstrated that the combined therapy induced a stronger inhibition of the tumor growth compared to both formulations administered separately. The molecular mechanisms underlying this antitumor effect of the combined therapy are based on the inhibition of C-Jun and MMP-2 activation. Also, the combined therapy induced a stronger inhibition of two important proangiogenic proteins: VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor). In conclusion, our data indicated that LCL-PLP enhanced the therapeutic outcome of LCL-DOX and this therapy could be promising for the treatment of metastatic melanoma.
- Subjects
DOXORUBICIN; FIBROBLAST growth factor 2; VASCULAR endothelial growth factors; MELANOMA; ANTINEOPLASTIC agents; PREDNISOLONE
- Publication
Journal of Experimental & Molecular Biology, 2019, Vol 20, Issue 3, p20
- ISSN
2601-6974
- Publication type
Article