oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2018-17-4-67-74oncotomsk-818Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESВЛИЯНИЕ ТРАНСКРИПЦИОННЫХ ФАКТОРОВ, VEGF И ПРОТЕИНАЗ НА прогрессирование РАКА ПОЧКИIMPACT OF TRANSCRIPTION FACTORS, VEGF AND PROTEASES ON KIDNEY CANCER PROGRESSIONСпиринаЛ. В.SpirinaL. V.

Россия, 634009, г. Томск, пер. Кооперативный, 5

Россия, 634050, г. Томск, Московский тракт, 2

доктор медицинских наук, старший научный сотрудник лаборатории биохимии опухолей, Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук

SPIN-код: 1336-8363. AuthorID (РИНЦ): 441893. ResearcherID (WOS): A-7760-2012. AuthorID (Scopus): 36960462500

5, Kooperativny street, 634009-Tomsk, Russia

2, Moskovsky trakt, 634050-Tomsk, Russia

MD, DSc, Senior Researcher of Laboratory of Tumor Biology, Cancer Research Institute, Tomsk National Research Medical  Center, Russian Academy of Sciences; Professor, Siberian  State Medical university

ResearcherID (WOS): A-7760-2012. AuthorsID (Scopus): 36960462500

spirinalv@oncology.tomsk.ruhttps://orcid.org/0000-0002-0947-8778КондаковаИ. В.KondakovaI. V.

Россия, 634009, г. Томск, пер. Кооперативный, 5

доктор медицинских наук, профессор, заведующая лабораторией биохимии опухолей, Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук

SPIN-код: 9338-4149. AuthorID (РИНЦ): 349081. AuthorID (Scopus): 6701872510. ResearcherID (WOS): C-8658-2012

5, Kooperativny street, 634009-Tomsk, Russia

MD, DSc, Professor, Head of Laboratory of Tumor Biochemistry, Cancer Research Institute, Tomsk NationalResearch Medical Center, Russian Academy of Sciences 

AuthorsID (Scopus): 6701872510. ResearcherID (WOS): C-8658-2012.

kondakova@oncology.tomsk.ruУсынинЕ. А.UsyninE. A.

Россия, 634009, г. Томск, пер. Кооперативный, 5

кандидат медицинских наук, научный сотрудник отделения общей онкологии, Научно- исследовательский институт онкологии, Томский национальный  исследовательский медицинский центр Российской академии наук 

SPIN-код: 1804-0292

5, Kooperativny street, 634009-Tomsk, Russia

MD, DSc, Senior Researcher, Department of General Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Author ID (Scopus): 56204320500

gusi@list.ruhttps://orcid.org/0000-0003-4382-5697СлонимскаяЕ. М.SlonimskayaE. M.

Россия, 634009, г. Томск, пер. Кооперативный, 5

доктор медицинских наук, профессор, руководитель отделения общей онкологии, Научно- исследовательский институт онкологии, Томский национальный исследовательский  медицинский центр Российской академии наук 

SPIN-код: 7763-6417. AuthorID (РИНЦ): 183823. AuthorID (Scopus): 6603658443. ResearcherID (WOS): C-7405-2012

5, Kooperativny street, 634009-Tomsk, Russia

2, Moskovsky trakt, 634050-Tomsk, Russia

MD, DSc, Professor, Head of General Oncology Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

AuthorsID (Scopus): 6603658443. ResearcherID (WOS): C-7405-2012

slonimskaya@yandex.ruЮрмазовЗ. А.YurmazovZ. A.

Россия, 634009, г. Томск, пер. Кооперативный, 5

Россия, 634050, г. Томск, Московский тракт, 2

врач, Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук 

SPIN-код: 6342-8935. AuthorID (РИНЦ): 557929

5, Kooperativny street, 634009-Tomsk, Russia

MD, DSc, physician, Department of General Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

goorbunov@gmail.comНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences Siberian State Medical UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian Federation2018020920181746774Copyright © Спирина Л.В., Кондакова И.В., Усынин Е.А., Слонимская Е.М., Юрмазов З.А., 20182018Спирина Л.В., Кондакова И.В., Усынин Е.А., Слонимская Е.М., Юрмазов З.А.Spirina L.V., Kondakova I.V., Usynin E.A., Slonimskaya E.M., Yurmazov Z.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/818Введение

Введение. Эффективность противоракового лечения зависит от биологических факторов опухоли.

Цель исследования – определить активность протеасом и кальпаинов и выявить их связь с содержанием  VEGF, HIF-1α и NF-κΒ в опухолевых, неизмененных и метастатических тканях карциномы почек (RCC).

Материал и методы

Материал и методы. В исследование были включены 93 пациента с почечно-клеточным раком. Содержание  транскрипционных факторов и VEGF определяли методом ИФА. Количественный состав протеасом исследовали  методом Вестерн-блоттинг. Активность протеасомы и кальпаина определяли с использованием специфического флюорогенного субстрата.

Результаты

Результаты. Выявлена инактивация протеолиза у пациентов с раком почки. Прогрессирование заболевания  было связано со значительным снижением уровня клеточного протеолиза и ростом содержания  транскрипционных и ростовых факторов в тканях первичной опухоли. Активация протеолиза была обнаружена в метастатических тканях.

Выводы

Выводы. В результате проведенного исследования показано, что факторы транскрипции NF-κΒ, HIF-1α, VEGF и внутриклеточные протеолитические системы участвуют в прогрессировании рака почки.

Introduction

Introduction. The efficacy of anticancer treatment depends on biological factors of tumor.

The aim of the study was to determine the activity of proteasomes and calpains and to  reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues.

Methods

Methods. Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEGF were measured using ELISA kits. The  levels of proteasome subunits were measured by Western Blotting. Proteasome and calpain  activities were determined using specific fluorogenic  substrates.

Results

Results. We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in  transcription and growth factor levels in primary kidney cancer tissues. The proteolysis  activation was found in metastatic tissues.

Conclusions

Conclusions. Our results suggest that NF-κΒ, HIF-1α and VEGF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.

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The authors declare that there are no conflicts of interest present.