oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-5-68-75oncotomsk-1580Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESВЛИЯНИЕ ХРОНИЧЕСКОЙ НЕЙРОГЕННОЙ БОЛИ НА ВОЗНИКНОВЕНИЕ И РОСТ САРКОМЫ М1 В ЛЕГКОМ КРЫС ПУТЕМ ИЗМЕНЕНИЯ ЛОКАЛЬНОГО СОДЕРЖАНИЯ ФАКТОРОВ РОСТАCHRONIC NEUROGENIC PAIN PROMOTES DEVELOPMENT AND GROWTH OF M1 SARCOMA CHANGING LOCAL LEVELS OF GROWTH FACTORShttps://orcid.org/0000-0003-3618-6890ФранциянцЕ. М.FrantsiyantsE. M.

доктор биологических наук, профессор, заместитель генерального директора по науке, руководитель лаборатории изучения патогенеза злокачественных опухолей,

344037, г. Ростов-на-Дону, ул. 14 линия, 63

DSc, Professor, Deputy General Director for Science, Head of Laboratory of Malignant Tumor Pathogenesis Study,

63, 14 Liniya Street, 344037-Rostov-on-Don

https://orcid.org/0000-0002-2302-8271БандовкинаВ. А.BandovkinaV. A.

кандидат биологических наук, старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей,

344037, г. Ростов-на-Дону, ул. 14 линия, 63

PhD, Senior Researcher, Laboratory of Malignant Tumor Pathogenesis Study,

63, 14 Liniya Street, 344037-Rostov-on-Don

valerryana@yandex.ruhttps://orcid.org/0000-0002-3972-2452КаплиеваИ. В.KaplievaI. V.

доктор медицинских наук, старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей,

344037, г. Ростов-на-Дону, ул. 14 линия, 63

DSc, Senior Researcher, Laboratory of Malignant Tumor Pathogenesis Study,

63, 14 Liniya Street, 344037-Rostov-on-Don

https://orcid.org/0000-0002-9749-2747ТрепитакиЛ. К.TrepitakiL. K.

лаборант-исследователь лаборатории изучения патогенеза злокачественных опухолей,

344037, г. Ростов-на-Дону, ул. 14 линия, 63

Research Assistant, Laboratory of Malignant Tumor Pathogenesis Study, 

63, 14 Liniya Street, 344037-Rostov-on-Don

https://orcid.org/0000-0002-3711-8155ЧеряринаН. Д.CheryarinaN. D.

врач-лаборант лаборатории изучения патогенеза злокачественных опухолей,

344037, г. Ростов-на-Дону, ул. 14 линия, 63

Laboratory Assistant, Laboratory of Malignant Tumor Pathogenesis Study, 

63, 14 Liniya Street, 344037-Rostov-on-Don

https://orcid.org/0000-0002-7395-3086НескубинаИ. В.NeskubinaI. V.

кандидат биологических наук, старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей,

344037, г. Ростов-на-Дону, ул. 14 линия, 63

PhD, Senior Researcher, Laboratory of Malignant Tumor Pathogenesis Study,

63, 14 Liniya Street, 344037-Rostov-on-Don

ФГБУ «НМИЦ онкологии» Минздрава РФРоссияNational Medical Research Centre for OncologyRussian Federation2020281020201956875Copyright © Франциянц Е.М., Бандовкина В.А., Каплиева И.В., Трепитаки Л.К., Черярина Н.Д., Нескубина И.В., 20202020Франциянц Е.М., Бандовкина В.А., Каплиева И.В., Трепитаки Л.К., Черярина Н.Д., Нескубина И.В.Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V., Trepitaki L.K., Cheryarina N.D., Neskubina I.V.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/1580Введение

Введение. Влияние хронической нейрогенной боли (ХНБ) на локальное содержание факторов роста в легком и возможность развития в нем злокачественного процесса практически не исследованы.

Целью исследования явилось изучение уровней VEGF, TGF-β, IGF-I, IGF-II, FGF-21 и рецепторов VEGFR2, TGF-βR2 в легких белых беспородных крыс с внутривенным введением саркомы М1 на фоне хронической нейрогенной боли.

Материал и методы

Материал и методы. Эксперимент проводили на 28 белых беспородных крысах-самцах массой 200–250 г. Животные были разделены на 4 группы: 1 – ложно оперированные животные (контрольная группа) (n=7); 2 – животные с воспроизведенной хронической нейрогенной болью (n=7); 3 – ложно оперированные животные с внутривенным введением саркомы М1 (n=7); 4 – крысы с внутривенным введением саркомы М1 на фоне хронической нейрогенной боли (n=7). Животных умерщвляли декапитацией, на льду извлекали легкие, получали 10 % цитозольные фракции на 0,1М калий-фосфатном буфере рН 7,4, содержащем 0,1 % Твин-20 и 1 % БСА. Методами иммуноферментного анализа (ИФА) определяли концентрацию VEGFR2, TGF-β, его рецептора TGFβR2, IGF-I, IGF-II (CUSABIO BIOTECH Co., Ltd., Китай) и FGF21 (BioVender, Чехия). Статистическую обработку результатов проводили с помощью программы Statistica 10.0.

Результаты

Результаты. Только в группе крыс с ХНБ в легких после внутривенной перевивки саркомы М1 определялись многофокусные опухолевые очаги саркомы. В легких ложно оперированных крыс после перевивки М1 опухолевые очаги не были обнаружены. В ткани легкого при росте М1 под действием ХНБ установлено снижение уровня VEGF-А, но повышение остальных TGFβ, IGF-I, IGF-II и FGF-21. ХНБ прямо или опосредованно повлияла на содержание в легком ряда факторов роста, а также изменила клеточный гомеостаз, сделав возможным возникновение опухоли после перевивки в легкое саркомы М1. 

Introduction

Introduction. The influence of chronic neurogenic pain on local levels of growth factors in the lung and the risk of lung cancer development has been little studied.

The purpose of the study was to analyze the levels of VEGF, TGF-β, IGF-I, IGF-II, FGF-21 and receptors of VEGFR2, TGF-βR2 in the lungs of white outbred rats with chronic neurogenic pain after intravenous injection of M1 sarcoma.

Material and Methods

Material and Methods. A total of 28 white outbred male rats weighing 200–250 g were divided into 4 groups: 1 – sham-operated animals (control group) (n=7); 2 – animals with chronic neurogenic pain (n=7); 3 – sham-operated animals with intravenous injection of M1 sarcoma (n=7); 4 – rats with intravenous injection of M1 sarcoma in presence of chronic neurogenic pain (n=7). Animals were decapitated, the lungs were harvested on ice; 10 % cytosolic fractions were prepared in 0.1 M potassium phosphate buffer pH 7.4 containing 0.1 % Tween-20 and 1 % BSA. Levels of VEGFR2, TGF-β and receptors of TGF-βR2, IGF-I, IGF-II (CUSABIO BIOTECH Co., Ltd., China) and FGF21 (BioVender, Czech Republic) were determined by ELISA. The data were statistically processed using Statistica 10.0 software.

Results

Results. Multifocal tumors of sarcoma in the lungs were determined only in the group of rats with chronic neurogenic pain after intravenous transplantation of M1 sarcoma. In the lungs of sham-operated animals, tumor foci were not detected after M1 sarcoma transplantation. Lung tissues with M1 growth and presence of chronic neurogenic pain demonstrated decreased VEGF-А levels with increased concentrations of TGFβ, IGF-I, IGF-II and FGF-21. Chronic neurogenic pain directly or indirectly influenced levels of some growth factors in the lung, and altered cell homeostasis making possible transplantation of M1 sarcoma into the lung. 

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