antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2021-66-9-10-17-23antibiotics-855Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИExperimental ResearchКомбинация наносомальной формы доксорубицина, интерферона альфа и нитроглицерина в терапии крыс Вистар с глиобластомой 101.8Combination of nanosomal form of doxorubicin, interferon alpha, and nitroglycerin in the threatment of 101.8 glioblastoma in Wistar ratsКуделькинаВ. В.KudelkinaV. V.

Куделькина Вера Владимировна — научный сотрудник лаборатории нейроморфологии

Москва

Vera V. Kudelkina — Researcher

Moscow

verakudelkina8047@gmail.comХаланскийА. С.KhalanskyA. S.

Халанский Александр Сергеевич — к. б. н., ведущий научный сотрудник лаборатории нейроморфологии

Москва

Alexander S. Khalansky — Ph. D. in biology

Moscow

АлексееваА. И.AlekseevaA. I.

Алексеева Анна Игоревна — младший научный сотрудник лаборатории нейроморфологии

Москва

Anna I. Alekseeva — Junior Researcher

Moscow

ГореликовП. Л.GorelikovP. L.

Гореликов Петр Леонидович — д. б. н., старший научный сотрудник лаборатории нейроморфологии

Москва

Petr L. Gorelikov — D. Sc. in biology

Moscow

КосыреваА. М.KosyrevaA. M.

Косырева Анна Михайловна — д. б. н., заведующая лабораторией нейроморфологии

Москва

Anna M. Kosyreva — D. Sc. in biology

Moscow

ФГБНУ НИИ морфологии человека им. академика А. П. АвцынаРоссияA. P. Avtsyn Research Institute of Human MorphologyRussian Federation202102012022669-101723Copyright © Куделькина В.В., Халанский А.С., Алексеева А.И., Гореликов П.Л., Косырева А.М., 20222022Куделькина В.В., Халанский А.С., Алексеева А.И., Гореликов П.Л., Косырева А.М.Kudelkina V.V., Khalansky A.S., Alekseeva A.I., Gorelikov P.L., Kosyreva A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/855

Поиск эффективных подходов лечения пациентов с глиобластомой является одной из сложных задач нейроонкологии, стандартные методы терапии показывают ограниченные результаты. Комбинированная терапия, включающая разные противоопухолевые механизмы, позволяет повысить её эффективность. В нашей работе исследовали сочетание PLGA-наноформы доксорубицина (Докс-PLGA), противоопухолевого цитокина — интерферона α (ИФНα) и донора оксида азота (NO) нитроглицерина (НГ) как в системе in vitro (глиома С6 крысы), так и in vivo (глиобластома 101.8, крысы). МТТ-анализ на клеточной культуре С6 показал большую цитотоксичность и антипролиферативный эффект комбинации ИФНα с Докс-PLGA и НГ. Наименьшую выживаемость опухолевых клеток наблюдали при использовании высокой дозы ИФНα (10 нг/мл) в монорежиме. В эксперименте in vivo 32 самкам крыс Вистар с глиобластомой 101.8 проводили терапию в следующих режимах: Докс-PLGA+НГ; ДоксPLGA+ИФНα; Докс-PLGA+ИФНα+НГ. Для всех групп с терапией отмечено достоверное увеличение медианной выживаемости и продолжительности жизни (УПЖ) относительно группы без лечения. Наибольшую медианную продолжительность жизни (27 сут), выживаемость до 100 сут (1 животное), УПЖ (131%) наблюдали у животных, получавших комбинацию Докс-PLGA+ИФНα+НГ, по сравнению с группой без лечения, в которой медианная продолжительность жизни составила 15 сут. Таким образом, терапия экспериментальной глиобластомы как в системе in vivo, так и in vitro комбинацией Докс-PLGA+ИФНα+НГ оказывает наиболее выраженный терапевтический и противоопухолевый эффект, что необходимо учитывать при разработке новых более эффективных методов лечения глиобластом человека.

The search for effective approaches to the treatment of patients with glioblastoma is one of the difficult tasks of neurooncology; standard methods of therapy show limited results. Combined therapy, which includes different antitumor mechanisms, can increase its effectiveness. The combination of PLGA nanoform of doxorubicin (Dox-PLGA), antitumor cytokine — interferon alfa (IFN-α), and nitrogen oxide (NO) donor nitroglycerin (NG) was investigated in this work both in vitro (rat C6 glioma) and in vivo (rat 101.8 glioblastoma). MTT assay in the C6 cell line showed great cytotoxicity and antiproliferative effect of the combination of IFN-α with Dox-PLGA and NG. The lowest tumour cell survival was observed when using a high dose of IFN-α (10 ng/ml) in mono-mode. In the in vivo experiment, 32 female Wistar rats with 101.8 glioblastoma received therapy in the following modes: Dox-PLGA + NG; Dox-PLGA + IFN-α; Dox- PLGA + IFN-α + NG. There was a significant increase in median survival and life expectancy (ILE) in all groups receiving therapy compared to the group that did not undergo treatment. The longest median lifespan (27 days), survival up to 100 days (1 animal), ILE (131%) were observed in animals that received the combination Dox-PLGA + IFN-α+ NG, compared to the group without treatment, in which the median lifespan was 15 days. Thus, the therapy of experimental glioblastoma both in vivo and in vitro with the combination of Dox-PLGA + IFN-α + NG has the most pronounced therapeutic and antitumor effect, which must be taken into account when developing new more effective methods of treating human glioblastomas.

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