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Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment

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 impo...

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Autores principales: Licarete, Emilia, Rauca, Valentin Florian, Luput, Lavinia, Drotar, Denise, Stejerean, Ioana, Patras, Laura, Dume, Bogdan, Toma, Vlad Alexandru, Porfire, Alina, Gherman, Claudia, Sesarman, Alina, Banciu, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215436/
https://www.ncbi.nlm.nih.gov/pubmed/32340166
http://dx.doi.org/10.3390/ijms21082968
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author Licarete, Emilia
Rauca, Valentin Florian
Luput, Lavinia
Drotar, Denise
Stejerean, Ioana
Patras, Laura
Dume, Bogdan
Toma, Vlad Alexandru
Porfire, Alina
Gherman, Claudia
Sesarman, Alina
Banciu, Manuela
author_facet Licarete, Emilia
Rauca, Valentin Florian
Luput, Lavinia
Drotar, Denise
Stejerean, Ioana
Patras, Laura
Dume, Bogdan
Toma, Vlad Alexandru
Porfire, Alina
Gherman, Claudia
Sesarman, Alina
Banciu, Manuela
author_sort Licarete, Emilia
collection PubMed
description 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.
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spelling pubmed-72154362020-05-18 Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment Licarete, Emilia Rauca, Valentin Florian Luput, Lavinia Drotar, Denise Stejerean, Ioana Patras, Laura Dume, Bogdan Toma, Vlad Alexandru Porfire, Alina Gherman, Claudia Sesarman, Alina Banciu, Manuela Int J Mol Sci Article 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. MDPI 2020-04-23 /pmc/articles/PMC7215436/ /pubmed/32340166 http://dx.doi.org/10.3390/ijms21082968 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Licarete, Emilia
Rauca, Valentin Florian
Luput, Lavinia
Drotar, Denise
Stejerean, Ioana
Patras, Laura
Dume, Bogdan
Toma, Vlad Alexandru
Porfire, Alina
Gherman, Claudia
Sesarman, Alina
Banciu, Manuela
Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
title Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
title_full Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
title_fullStr Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
title_full_unstemmed Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
title_short Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
title_sort overcoming intrinsic doxorubicin resistance in melanoma by anti-angiogenic and anti-metastatic effects of liposomal prednisolone phosphate on tumor microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215436/
https://www.ncbi.nlm.nih.gov/pubmed/32340166
http://dx.doi.org/10.3390/ijms21082968
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