antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-91Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSВлияние донора оксида азота на противоопухолевую активность доксорубицина в отношении экспериментальной глиобластомы крысPotentiating Effect of Nitric Oxide Donor on Antitumor Activity of Doxorubicin in Glioblastoma-Bearing RatsАлексееваА. И.AlekseevaA. I.mariott@bk.ruХаланскийА. С.KhalanskyA. S'.noemail@neicon.ruФедосееваВ. В.FedoseevaV. V.noemail@neicon.ruГореликовП. Л.GorelikovP. L.noemail@neicon.ruГельперинаС. Э.GelperinaS. E.noemail@neicon.ruНИИ морфологии человека; Первый московский государственный медицинский университет им. И. М. СеченоваРоссияResearch Institute of Human Morphology; I. M. Sechenov First Moscow State Medical UniversityRussian FederationНИИ морфологии человекаРоссияResearch Institute of Human MorphologyRussian FederationООО «Технология лекарств»РоссияLLC «Drugs Technology»Russian Federation201806052020637-81721Copyright © Алексеева А.И., Халанский А.С., Федосеева В.В., Гореликов П.Л., Гельперина С.Э., 20202020Алексеева А.И., Халанский А.С., Федосеева В.В., Гореликов П.Л., Гельперина С.Э.Alekseeva A.I., Khalansky A.S., Fedoseeva V.V., Gorelikov P.L., Gelperina S.E.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/91

Цель исследования - оценка противоопухолевого эффекта комбинации доксорубицина (Докс) и донора NO нитроглицерина (НГ) в отношении глиобластомы 101.8 у крыс. Материалы и методы. Глиобластому 101.8 имплантировали интракраниально самцам крыс Wistar. Животных рандомизировали по группам и вводили следующие препараты (n=15-19): 1) доксорубицин (Докс, 1,5 мг/кг, в/в), 2) нитроглицерин (НГ, масляный раствор, 5 мг/кг, наружно), 3) доксорубицин (Докс+НГ, 1,5 мг/кг, в/в) + нитроглицерин (5 мг/кг, наружно). Лечение проводили на 2-й, 5-й и 8-й дни после имплантации опухоли. Животных наблюдали в течение 100 дней. Размер опухоли определяли гистологическим методом на 14-й день (n=6-9). В качестве контроля использовали нелеченных животных. Результаты. Результаты лечения оценивали по увеличению продолжительности жизни (УПЖ, %) и торможению роста опухоли (ТРО, %). Увеличение продолжительности жизни было отмечено во всех группах. Максимальный эффект был достигнут в группе Докс+НГ: УПЖ - 176%, ТРО - 89%. В группе Докс УПЖ составило 130%, ТРО - 75%. УПЖ при терапии нитроглицерином составило 130%. Вывод. На модели экспериментальной глиобластомы 101.8 у крыс показано повышение противоопухолевого эффекта доксорубицина при сочетанном применении с донором оксида азота нитроглицерином. Этот феномен, вероятно, обусловлен более эффективным проникновением доксорубицина в опухоль в результате воздействия монооксида азота на церебральные сосуды.

The objective of the study was to investigate the influence of the NO donor nitroglycerin (NG) on the antitumour effect of doxorubicin (Dox) in rats with the intracranially implanted 101.8 glioblastoma. Materials and methods. Male Wistar rats with the implanted 101.8 glioblastoma were treated with the following formulations (n=15-19): doxorubicin (Dox, 1.5 mg/kg, i.v.), nitroglycerin (NG, 5 mg/kg, oil solution, topical), and a combination of doxorubicin and nitroglycerin (Dox+NG: 1.5 mg/kg and 5 mg/kg, respectively) on 2nd, 5th, and 8th day after tumor implantation. The tumor size was measured on the histological sections of the brain on the 14th day (n=6-9). The remaining animals were followed up for survival for 100 days. Untreated animals were used as control (n=22). Results. The antitumor effect was evaluated by the increase in life expectancy (ILE, %) and tumor growth inhibition (TGI, %) relative to untreated animals in control group. The increased life expectancy was observed in all groups. The maximal effect was achieved in the Dox+NG group: ILE 176%, TGI 89%. In the Dox group, the ILE was 130% and TGI was 75%. Nitroglycerin alone produced the ILE of 130%. Conclusion. Nitric oxide donor nitroglycerin considerably potentiated the antitumor activity of doxorubicin against the intracranial glioblastoma in rats. This phenomenon is most probably explained by the increased penetration of doxorubicin into the tumor due to the enhanced permeability of the cerebral endothelium produced by NO generated by nitroglycerin.

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