Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma

Study was aimed to analyze the dynamics of changes and study interrelations between content of ferritin, transferrin, active gelatina­ses (MMP-2 and -9) in blood serum and tumor tissue, free iron, rate of superoxide radicals generation in tumor, activity of NADPH-oxidase and iNOS in neutrophils rats...

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Бібліографічні деталі
Опубліковано в: :Experimental Oncology
Дата:2015
Автори: Burlaka, A.P., Ganusevich, I.I., Lozovska, Yu.V., Lukianova, N.Yu., Chekhun, V.F.
Формат: Стаття
Мова:Англійська
Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2015
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Онлайн доступ:https://nasplib.isofts.kiev.ua/handle/123456789/145452
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Цитувати:Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma / A.P. Burlaka, I.I. Ganusevich, Yu.V. Lozovska, N.Yu. Lukianova, V.F. Chekhun // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 36-39. — Бібліогр.: 31 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
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author Burlaka, A.P.
Ganusevich, I.I.
Lozovska, Yu.V.
Lukianova, N.Yu.
Chekhun, V.F.
author_facet Burlaka, A.P.
Ganusevich, I.I.
Lozovska, Yu.V.
Lukianova, N.Yu.
Chekhun, V.F.
citation_txt Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma / A.P. Burlaka, I.I. Ganusevich, Yu.V. Lozovska, N.Yu. Lukianova, V.F. Chekhun // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 36-39. — Бібліогр.: 31 назв. — англ.
collection DSpace DC
container_title Experimental Oncology
description Study was aimed to analyze the dynamics of changes and study interrelations between content of ferritin, transferrin, active gelatina­ses (MMP-2 and -9) in blood serum and tumor tissue, free iron, rate of superoxide radicals generation in tumor, activity of NADPH-oxidase and iNOS in neutrophils rats with sensitive and resistant strains of Guerin carcinoma (GC). Materials and Methods: In order to obtain resistant tumor, 12 courses of cisplatin chemotherapy have been carried out on rats bearing GC. Levels of transferrin and free iron were determined by analysis of EPR spectra from computerized radiospectrometer EPR ­RE-1307 at temperature of liquid nitrogen. Rate of superoxide radicals and nitric oxide generation in tumor and neutrophils of blood was determined by EPR using spin traps at room temperature. Content of ferritin in tumor homogenate and blood serum of rats with GC was determined by ELISA method using corresponding kits. Concentration of active forms of MMP-2 and -9 in obtained samples was determined using method of zymography. Results: Unregulated generation of superoxide radicals and NO by mitochondria of tumor cells and NADPH-oxidase and iNOS neutrophils via oxidation of iron-containing proteins causes the accumulation of “free iron” complexes in blood and tumor tissue of rats able to evoke oxide-induced damages of macromolecules. It has been shown that for resistant strain of carcinoma, as compared with sensitive one, significantly higher concentrations of active forms of MMP-2 and -9 in blood serum of rats are typical. Dynamics of gelatinases activity changes in tumor tissue corresponds in general with dynamics of changes in serum. In tumor tissue of rats the indices of gelatinases activity positively correlate with rate of superoxide radicals generation, content of “free iron” complexes, ferritin and activity of transferrin. Cytostatic agent increased levels of reactive oxygen species (ROS) and self-amplify rate of superoxide radicals generation. In turn, activation of MMPs via superoxide-depending regulation allows tumor cells to facilitate migration, invasion and finally — formation of metastatic centers. Mentioned above tumor “oxide phenotype” determines high level of its aggressiveness and forms corresponding level of drug resistance. Conclusions: Thus, high levels of superoxide radicals oxidize transport proteins and form free iron pool. Iron ions, via Haber — Weiss mechanism, initiate generation of the hydroxyl radicals, which also enhance oxidation processes. Key Words: drug resistance, redox-regulation, iron-containing proteins, matrix metalloproteinases.
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publishDate 2015
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
record_format dspace
spelling Burlaka, A.P.
Ganusevich, I.I.
Lozovska, Yu.V.
Lukianova, N.Yu.
Chekhun, V.F.
2019-01-21T21:25:34Z
2019-01-21T21:25:34Z
2015
Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma / A.P. Burlaka, I.I. Ganusevich, Yu.V. Lozovska, N.Yu. Lukianova, V.F. Chekhun // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 36-39. — Бібліогр.: 31 назв. — англ.
1812-9269
https://nasplib.isofts.kiev.ua/handle/123456789/145452
Study was aimed to analyze the dynamics of changes and study interrelations between content of ferritin, transferrin, active gelatina­ses (MMP-2 and -9) in blood serum and tumor tissue, free iron, rate of superoxide radicals generation in tumor, activity of NADPH-oxidase and iNOS in neutrophils rats with sensitive and resistant strains of Guerin carcinoma (GC). Materials and Methods: In order to obtain resistant tumor, 12 courses of cisplatin chemotherapy have been carried out on rats bearing GC. Levels of transferrin and free iron were determined by analysis of EPR spectra from computerized radiospectrometer EPR ­RE-1307 at temperature of liquid nitrogen. Rate of superoxide radicals and nitric oxide generation in tumor and neutrophils of blood was determined by EPR using spin traps at room temperature. Content of ferritin in tumor homogenate and blood serum of rats with GC was determined by ELISA method using corresponding kits. Concentration of active forms of MMP-2 and -9 in obtained samples was determined using method of zymography. Results: Unregulated generation of superoxide radicals and NO by mitochondria of tumor cells and NADPH-oxidase and iNOS neutrophils via oxidation of iron-containing proteins causes the accumulation of “free iron” complexes in blood and tumor tissue of rats able to evoke oxide-induced damages of macromolecules. It has been shown that for resistant strain of carcinoma, as compared with sensitive one, significantly higher concentrations of active forms of MMP-2 and -9 in blood serum of rats are typical. Dynamics of gelatinases activity changes in tumor tissue corresponds in general with dynamics of changes in serum. In tumor tissue of rats the indices of gelatinases activity positively correlate with rate of superoxide radicals generation, content of “free iron” complexes, ferritin and activity of transferrin. Cytostatic agent increased levels of reactive oxygen species (ROS) and self-amplify rate of superoxide radicals generation. In turn, activation of MMPs via superoxide-depending regulation allows tumor cells to facilitate migration, invasion and finally — formation of metastatic centers. Mentioned above tumor “oxide phenotype” determines high level of its aggressiveness and forms corresponding level of drug resistance. Conclusions: Thus, high levels of superoxide radicals oxidize transport proteins and form free iron pool. Iron ions, via Haber — Weiss mechanism, initiate generation of the hydroxyl radicals, which also enhance oxidation processes. Key Words: drug resistance, redox-regulation, iron-containing proteins, matrix metalloproteinases.
en
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
Experimental Oncology
Original contributions
Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
Article
published earlier
spellingShingle Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
Burlaka, A.P.
Ganusevich, I.I.
Lozovska, Yu.V.
Lukianova, N.Yu.
Chekhun, V.F.
Original contributions
title Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
title_full Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
title_fullStr Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
title_full_unstemmed Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
title_short Redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant Guerin carcinoma
title_sort redox-regulation of gelatinases during growth of cisplatin-sensitive and resistant guerin carcinoma
topic Original contributions
topic_facet Original contributions
url https://nasplib.isofts.kiev.ua/handle/123456789/145452
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AT ganusevichii redoxregulationofgelatinasesduringgrowthofcisplatinsensitiveandresistantguerincarcinoma
AT lozovskayuv redoxregulationofgelatinasesduringgrowthofcisplatinsensitiveandresistantguerincarcinoma
AT lukianovanyu redoxregulationofgelatinasesduringgrowthofcisplatinsensitiveandresistantguerincarcinoma
AT chekhunvf redoxregulationofgelatinasesduringgrowthofcisplatinsensitiveandresistantguerincarcinoma