rpmjResearch'n Practical Medicine JournalResearch and Practical Medicine Journal2410-1893"QUASAR", LLC10.17709/2409-2231-2020-7-4-3rpmj-630Research ArticleОригинальные статьи. Онкология, лучевая терапияOriginal Articles. ОncologyСодержание факторов роста в лёгких при их злокачественном поражении и профилактическом действии 1,3-диэтилбензимидазолия трийодида в экспериментеLevels of growth factors in the lungs affected by cancer with preventive effect of 1,3-diethylbenzimidazolium triiodide in the experimenthttps://orcid.org/0000-0003-3618-6890ФранциянцЕ. М.FrantsiyantsE. M.

Франциянц Елена Михайловна – д.б.н., профессор, заместитель генерального директора по научной работе, руководитель лаборатории изучения патогенеза злокачественных опухолей

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

SPIN: 9427-9928

AuthorID: 462868

Scopus Author ID: 55890047700

ResearcherID: Y-1491-2018

Elena M. Frantsiyants – Dr. Sci. (Biol.), professor, deputy director general for science, head of the laboratory for the study of malignant tumors pathogenesis 

63 14 line str., Rostov-on-Don 344037

SPIN: 9427-9928

AuthorID: 462868

Scopus Author ID: 55890047700

ResearcherID: Y-1491-2018

https://orcid.org/0000-0002-3972-2452КаплиеваИ. В.KaplievaI. V.

Каплиева Ирина Викторовна – д.м.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

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

SPIN: 5047-1541

AuthorID: 734116

Scopus Authorm ID: 23994000800

Researcher ID: AAE-3540-2019

Irina V. Kaplieva – Dr. Sci. (Med.), senior researcher at the laboratory for the study of malignant tumors pathogenesis 

63 14 line str., Rostov-on-Don 344037

SPIN: 5047-1541

AuthorID: 734116

Scopus Author ID: 23994000800

ResearcherID: AAE-3540-2019

kaplirina@yandex.ruhttps://orcid.org/0000-0002-9749-2747ТрепитакиЛ. К.TrepitakiL. K.

Трепитаки Лидия Константиновна – лаборант-исследователь лаборатории изучения патогенеза злокачественных опухолей

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

SPIN: 2052-1248

AuthorID: 734359

Scopus Author ID: 55357624700

ResearcherID: NAAG-9218-2019

Lidiya K. Trepitaki – laboratory assistant-researcher of the laboratory for the study of malignant tumors pathogenesis

63 14 line str., Rostov-on-Don 344037

SPIN: 2052-1248

AuthorID: 734359

Scopus Author ID: 55357624700

ResearcherID: NAAG-9218-2019

ФГБУ «НМИЦ онкологии» Минздрава РоссииРоссияNational Medical Research Centre for Oncology of the Ministry of Health of RussiaRussian Federation202021122020742735Copyright © Франциянц Е.М., Каплиева И.В., Трепитаки Л.К., 20202020Франциянц Е.М., Каплиева И.В., Трепитаки Л.К.Frantsiyants E.M., Kaplieva I.V., Trepitaki L.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpmj.ru/rpmj/article/view/630Цель исследования

Цель исследования. Изучить динамику VEGF-А, TGF-β и их рецепторов в ткани легкого крыс на фоне антиканцерогенного действия 1,3-диэтилбензимидазолия трийодида (Стелланина).

Материалы и методы

Материалы и методы. Исследование проведено на белых беспородных крысах массой 180–220 грамм. Основную группу составили самцы (n=27) и самки (n=27) с перевитой в подключичную вену, но не выросшей в лёгких, саркомой 45 (с45) (2×106 клеток в 0,5 мл физ. раствора) вследствие последующего внутрижелудочного введения Стелланина (0,4 мг/кг 1 раз в день) по прерывистой схеме: 5 дней — введение, 2 дня — перерыв. Контроль — самцы (n=14) и самки (n=14) без лечения с ростом с45 в лёгких. В интактные группы вошло по 5 крыс обоего пола. Через 4, 5 и 8 недель эксперимента крыс декапитировали, в 10% гомогенатах лёгких методом ИФА определяли: VEGF-A, sVEGF-R1, sVEGF-R2, TGF-β и sTGFβR2 (CUSABIO BIOTECH Co., Ltd., Китай).

Результаты

Результаты. У интактных самок в ткани лёгкого содержалось в 1,4 раза (р<0,05) меньше VEGF-А и в 3,3 раза больше sVEGF-R1, чему самцов. Формирование неоплазм в лёгких у всех контрольных крыс сопровождалось ростом VEGF-А (в 1,6–3,0 раза) и трёхкратной редукцией TGF-β. Динамика обоих рецепторов VEGF у самцов и самок была разнонаправленной. Количество sVEGF-R1 у самцов увеличивалось в 1,5 раза (р<0,05), у самок — уменьшалось в 1,8 раз (р<0,05) и, в результате, становилось одинаковым у всех животных. Содержание sVEGF-R2 у самцов двукратно уменьшалось, у самок — увеличивалось в 1,4 раза (р<0,05), как итог, у самок концентрация sVEGF-R2 становилась в 2,4 раза больше, чем у самцов. У 2/3 крыс Стелланин предупреждал развитие с45 в лёгких за счёт торможения роста VEGF-А — более чем в 2,0 раза и увеличения концентраций: sVEGF-R1 — в 10,0 раз и TGF-β — в 6,0 раз на фоне нормализации sVEGF-R2 и sTGFβR2.

Purpose of the study

Purpose of the study. Analyzing the dynamics of VEGF-А, TGF-β and their receptors in the lung tissues in rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide (Stellanin).

Material and methods

Material and methods. The study included white outbred rats weighing 180–220 g. The main group included males (n=27) and females (n=27) with sarcoma 45 (s45) inoculated into the subclavian vein but not developed in the lungs (2×106 cells in 0.5 ml of saline) due to the subsequent intragastric administration of Stellanin (0.4 mg/kg once a day) according to an intermittent scheme: administration for 5 days and a break for 2 days. The control group included males (n=14) and females (n=14) without treatment with growing s45 in the lungs. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of VEGF-A, sVEGF-R1, sVEGF-R2, TGF-β and sTGFβR2 were measured in 10% lung homogenates by ELISA (CUSABIO BIOTECH Co., Ltd., China).

Results

Results. Lung tissues of intact females showed 1.4 times (p<0.05) lower VEGF-А and 3.3 times higher sVEGF-R1, compared to males. The development of tumors in all control rats was accompanied by the VEGF-А increase (by 1.6–3.0 times) and the TGF-β reduction (by 3 times). The dynamics of both VEGF receptors differed in males and females. The levels of sVEGF-R1 in males increased by 1.5 times (p<0.05), while in females it decreased by 1.8 times (p<0.05), and as a result, the levels became similar in all animals. The levels of sVEGF-R2 in males decreased by 2 times, and in females it increased by 1.4 times (p<0.05), so the sVEGF-R2 content in females became 2.4 times higher than in males. In two-thirds of rats, Stellanin prevented s45 development in the lungs due to inhibition of VEGF-A growth by more than 2.0 times and an increase in concentrations of sVEGF-R1 by 10.0 times and TGF-β by 6.0 times, together with normalization of sVEGF-R2 and sTGFβR2.

Conclusions

Conclusions. Stellanin prevents the development of malignant process in the lungs by inhibiting neoangiogenesis (deficiency of VEGF-A and excess of sVEGF-R1) and suppressing the proliferation of malignant cells (TGF-β growth).

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