diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13224diaendo-13224Research ArticleОбзорыReviewИнгибиторы натрий-глюкозного котранспортера 2 типа как потенциальные противоонкогенные средстваSodium-glucose cotransporter 2 inhibitors as potential anticancer agentshttps://orcid.org/0000-0003-0206-0114РадкевичЕ. Р.RadkevichE. R.

Радкевич Елизавета Романовна, клинический ординатор 

117292, г. Москва, ул. Дм. Ульянова, д. 11 

Elizaveta R. Radkevich, clinical resident

11 Dmitriy Ulyanova street, 117292 Moscow

Lizysha99@mail.ruhttps://orcid.org/0000-0002-0296-4933СеверинаА. С.SeverinaA. S.

Северина Анастасия Сергеевна, к.м.н., в.н.с. 

Москва

Anastasia S. Severina, MD, PhD, leading research associate

Moscow

ansev1@mail.ruhttps://orcid.org/0000-0002-3433-0142ШамхаловаМ. Ш.ShamkhalovaM. S.

Шамхалова Минара Шамхаловна, д.м.н.

Москва

Minara S. Shamkhalova, MD, PhD

Moscow

shamkhalova@mail.ruhttps://orcid.org/0000-0002-5057-127XШестаковаМ. В.ShestakovaM. V.

Шестакова Марина Владимировна, д.м.н., профессор, академик РАН

Москва

Scopus Author ID: 7004195530

Marina V. Shestakova, MD, PhD, Professor, Academician of the RAS

Moscow

shestakova.mv@gmail.comГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии»РоссияEndocrinology Research CentreRussian Federation202523052025282243251Copyright © Радкевич Е.Р., Северина А.С., Шамхалова М.Ш., Шестакова М.В., 20252025Радкевич Е.Р., Северина А.С., Шамхалова М.Ш., Шестакова М.В.Radkevich E.R., Severina A.S., Shamkhalova M.S., Shestakova M.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.dia-endojournals.ru/jour/article/view/13224

Онкологические заболевания являются одной из ведущих причин смертности в мире. Несмотря на интенсивный поиск новых методов по увеличению эффективности и безопасности противоопухолевой терапии и снижению резистентности к ней со стороны злокачественных опухолей, вопросы лечения по-прежнему остаются открытыми в клинической онкологии. В данном обзоре произведен анализ экспериментальных данных, свидетельствующих об антинеопластическом эффекте ингибиторов натрий-глюкозного котранспортера 2 типа (иНГЛТ-2): приведены основания, по которым иНГЛТ-2 возможно использовать для лечения злокачественных опухолей, определена класс-специфичность и дозозависимость антинеопластического эффекта лекарственных препаратов. В деталях описаны возможные механизмы противоопухолевого эффекта глифлозинов, среди которых, помимо снижения поступления глюкозы в опухолевые клетки, существенную роль играют ингибирование сигнального пути Wnt/β-катенин, усиление активности АМФ-активируемой протеинкиназы с последующим изменением липидного профиля опухолевых клеток и ингибированием протеинкиназы mTOR (mammalian target of rapamycin), нарушение синтеза ДНК и РНК в клетках злокачественных опухолей и др. Значительное место уделено проонкогенному эффекту иНГЛТ-2, неоспоримому ранее и опровергнутому сегодня, а также взаимодействию данного класса противодиабетических средств с другими методами противоопухолевого лечения в контексте эффективности, безопасности и терапевтической резистентности.

Oncological diseases are one of the leading causes of mortality in the world. Despite the intensive search for new methods to increase the efficacy and safety of antineoplastic therapy and to reduce resistance to it by malignant tumors, treatment issues still remain unresolved in clinical oncology. This review analyses experimental data on the antineoplastic effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors: the reasons why SGLT2 inhibitors can be used for the treatment of malignant tumors are presented, class-specificity and dose-dependence of the antineoplastic effect of the drugs are determined. Possible mechanisms of antitumor effect of glyflozins are described in detail, among which, in addition to reduction of glucose entry into tumor cells, inhibition of Wnt/β-catenin signalling pathway, enhancement of AMP activated protein kinase activity with subsequent change of lipid profile of tumor cells and inhibition of mTOR protein kinase (mammalian target of rapamycin), disruption of DNA and RNA synthesis in malignant tumor cells, etc. play a significant role. Considerable space is devoted to the pro-oncogenic effect of SGLT2 inhibitors, previously undisputed and now disproved, as well as to the interaction of this class of antidiabetic agents with other antitumor treatment in the context of efficacy, safety and therapeutic resistance.

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