Autophagy activation in breast cancer cells in vitro after the treatment with PI3K/AKT/mTOR inhibitors

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Abstract

Introduction. Current chemotherapy of breast cancer has a wide range of disadvantages, in particular, the development of therapy-related infections and hormonal imbalance. Combination of main cytostatic with glucocorticoids allows to broaden its therapeutic interval and to decrease the total toxicity of the treatment. However, long-term treatment with glucocorticoids leads to the development of severe side effects via activation of multiple molecular mechanisms. Thus, glucocorticoids activate prosurvival mTOR-dependent autophagy. Therefore, the evaluation of PI3K (phosphoinositide 3-kinases) / Akt (protein kinase B) / mTOR (mammalian target of rapamycin) inhibitors as adjuvants for breast cancer therapy is important for optimization of treatment protocol.
Aim. Analysis of the effects of PI3K/Akt/mTOR inhibitors, rapamycin, wortmannin and LY-294002 in combination with glucocorticoids in breast cancer cell lines of different subtypes.
Materials and methods. We demonstrated the inhibition of PI3K/Akt/mTOR signaling and the autophagy induction after the treatment of breast cancer cells with rapamycin, wortmannin and LY-294002 by Western blotting analysis of Beclin-1, phospho-Beclin-1 (Ser93 and Ser30).
Conclusion. PI3K/Akt/mTOR inhibitors in combination with Dexamethasone cooperatively inhibited mTOR signaling and activated autophagy in breast cancer cells in vitro.

About the authors

D. D. Grigoreva

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: grigodidmit@gmail.com
ORCID iD: 0000-0003-2675-089X

Diana Dmitrievna Grigoreva

24 Kashirskoye Shosse, Moscow 115522

Russian Federation

E. M. Zhidkova

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-3318-9391

24 Kashirskoye Shosse, Moscow 115522

Russian Federation

E. S. Lylova

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-6388-1624

4 Kashirskoye Shosse, Moscow 115522

Russian Federation

A. D. Enikeev

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-7628-8616

24 Kashirskoye Shosse, Moscow 115522

Russian Federation

K. I. Kirsanov

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia; Peoples’ Friendship University of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-8599-6833

24 Kashirskoye Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

Russian Federation

G. A. Belitsky

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoye Shosse, Moscow 115522

Russian Federation

M. G. Yakubovskaya

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-9710-8178

24 Kashirskoye Shosse, Moscow 115522

Russian Federation

E. A. Lesovaya

N.N. Blokhin National Medical Russian Research Center of Oncology, Ministry of Health of Russia; I.P. Pavlov Ryazan State Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-1967-9637

24 Kashirskoye Shosse, Moscow 115522

9 Vysokovol’tnaya St., Ryazan 390026

Russian Federation

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