Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors

Abstract Vascular disrupting agents as DMXAA inhibit tumor growth only for a short period of time followed by rapid tumor regrowth. Among others, hypoxia and presence of transcription factor HIF-1α are responsible for tumors regrowth. The aim of our study was to investigate the inhibition of murine...

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Autores principales:	Ryszard Smolarczyk, Tomasz Cichoń, Ewelina Pilny, Magdalena Jarosz-Biej, Aleksandra Poczkaj, Natalia Kułach, Stanisław Szala
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ccfc0f6326849a7bf8f9fa6b0266d41
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spelling	oai:doaj.org-article:2ccfc0f6326849a7bf8f9fa6b0266d412021-12-02T16:07:50ZCombination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors10.1038/s41598-018-25688-y2045-2322https://doaj.org/article/2ccfc0f6326849a7bf8f9fa6b0266d412018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25688-yhttps://doaj.org/toc/2045-2322Abstract Vascular disrupting agents as DMXAA inhibit tumor growth only for a short period of time followed by rapid tumor regrowth. Among others, hypoxia and presence of transcription factor HIF-1α are responsible for tumors regrowth. The aim of our study was to investigate the inhibition of murine melanoma growth by combining two agents: anti-vascular - DMXAA and the HIF-1α inhibitor - digoxin and explaining the mechanism of action of this combination. After DMXAA treatment tumor size was reduced only for a limited time. After 7 days regrowth of tumors was observed and number of vessels was increased especially in tumor’s peripheral areas. DMXAA also induced an influx of immune cells: macrophages, CD8+ cytotoxic lymphocytes, NK cells, CD4+ lymphocytes. Administration of digoxin alone inhibited the growth of tumors. Administration of both agents in the proper sequence significantly inhibited the regrowth of tumors better than either agents alone. Combination therapy reduced number of newly formed vessels. In tumors of mice treated with combination therapy, the number of macrophages M1, CD8+ cytotoxic lymphocytes, NK cells and to a lesser extent CD4+ cells was increased. The combination of anti-vascular agents with HIF-1α inhibitors appears to be an effective therapeutic option.Ryszard SmolarczykTomasz CichońEwelina PilnyMagdalena Jarosz-BiejAleksandra PoczkajNatalia KułachStanisław SzalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryszard Smolarczyk Tomasz Cichoń Ewelina Pilny Magdalena Jarosz-Biej Aleksandra Poczkaj Natalia Kułach Stanisław Szala Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
description	Abstract Vascular disrupting agents as DMXAA inhibit tumor growth only for a short period of time followed by rapid tumor regrowth. Among others, hypoxia and presence of transcription factor HIF-1α are responsible for tumors regrowth. The aim of our study was to investigate the inhibition of murine melanoma growth by combining two agents: anti-vascular - DMXAA and the HIF-1α inhibitor - digoxin and explaining the mechanism of action of this combination. After DMXAA treatment tumor size was reduced only for a limited time. After 7 days regrowth of tumors was observed and number of vessels was increased especially in tumor’s peripheral areas. DMXAA also induced an influx of immune cells: macrophages, CD8+ cytotoxic lymphocytes, NK cells, CD4+ lymphocytes. Administration of digoxin alone inhibited the growth of tumors. Administration of both agents in the proper sequence significantly inhibited the regrowth of tumors better than either agents alone. Combination therapy reduced number of newly formed vessels. In tumors of mice treated with combination therapy, the number of macrophages M1, CD8+ cytotoxic lymphocytes, NK cells and to a lesser extent CD4+ cells was increased. The combination of anti-vascular agents with HIF-1α inhibitors appears to be an effective therapeutic option.
format	article
author	Ryszard Smolarczyk Tomasz Cichoń Ewelina Pilny Magdalena Jarosz-Biej Aleksandra Poczkaj Natalia Kułach Stanisław Szala
author_facet	Ryszard Smolarczyk Tomasz Cichoń Ewelina Pilny Magdalena Jarosz-Biej Aleksandra Poczkaj Natalia Kułach Stanisław Szala
author_sort	Ryszard Smolarczyk
title	Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
title_short	Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
title_full	Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
title_fullStr	Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
title_full_unstemmed	Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
title_sort	combination of anti-vascular agent - dmxaa and hif-1α inhibitor - digoxin inhibits the growth of melanoma tumors
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2ccfc0f6326849a7bf8f9fa6b0266d41
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Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors

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