Open Access
Cancers, volume 14, issue 18, pages 4396
Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy
Patutina Olga
1
,
Burakova Ekaterina
2, 3
,
Марков А. В.
1
,
Shmendel Elena
4
,
Maslov Michael
4
,
Стеценко Д.А.
2, 3
,
Vlassov Valentin
1
,
2
Publication type: Journal Article
Publication date: 2022-09-09
PubMed ID:
36139555
Cancer Research
Oncology
Abstract
Rational combinations of sequence-specific inhibitors of pro-oncogenic miRNAs can efficiently interfere with specific tumor survival pathways, offering great promise for targeted therapy of oncological diseases. Herein, we uncovered the potential of multicomponent therapy by double or triple combinations of highly potent mesyl phosphoramidate (µ) antisense oligodeoxynucleotides targeted to three proven pro-oncogenic microRNAs—miR-17, miR-21, and miR-155. A strong synergism in the inhibition of proliferation and migration of B16 melanoma cells was demonstrated in vitro for pairs of µ-oligonucleotides, which resulted in vivo in profound inhibition (up to 85%) of lung metastases development after intravenous injection of µ-oligonucleotide-transfected B16 cells in mice. A clear benefit of µ-21-ON/µ-17-ON and µ-17-ON/µ-155-ON/µ-21-ON combination antitumor therapy was shown for the lymphosarcoma RLS40 solid tumor model. In vivo administration of the µ-17-ON/µ-155-ON/µ-21-ON cocktail into RLS40-bearing mice elicited fourfold delay of tumor growth as a result of strong inhibition of tumor mitotic activity. It was discovered that the cocktail of µ-21-ON/µ-17-ON/µ-155-ON led to a twofold decrease in total destructive changes in murine liver, which indicates both the reduction in toxic tumor burden and the absence of specific toxicity of the proposed therapy.
Citations by journals
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Pharmaceutics
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Pharmaceutics
1 publication, 20%
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WIREs Mechanisms of Disease
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WIREs Mechanisms of Disease
1 publication, 20%
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Clinics
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Clinics, 1, 20%
Clinics
1 publication, 20%
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1
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Citations by publishers
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1
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 20%
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Wiley
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Wiley
1 publication, 20%
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Sao Paulo Universidade De Sao Paulo
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Sao Paulo Universidade De Sao Paulo, 1, 20%
Sao Paulo Universidade De Sao Paulo
1 publication, 20%
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1
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Gaponova S. et al. Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy // Cancers. 2022. Vol. 14. No. 18. p. 4396.
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Gaponova S., Patutina O., Sen’kova A. V., Burakova E., Savin I. A., Марков А. В., Shmendel E., Maslov M., Стеценко Д., Vlassov V., Зенкова М. А. Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy // Cancers. 2022. Vol. 14. No. 18. p. 4396.
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TY - JOUR
DO - 10.3390/cancers14184396
UR - https://doi.org/10.3390%2Fcancers14184396
TI - Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy
T2 - Cancers
AU - Patutina, Olga
AU - Burakova, Ekaterina
AU - Vlassov, Valentin
AU - Gaponova, Svetlana
AU - Sen’kova, Aleksandra V.
AU - Savin, Innokenty A.
AU - Марков, А. В.
AU - Shmendel, Elena
AU - Maslov, Michael
AU - Стеценко, Д.А.
AU - Зенкова, М. А.
PY - 2022
DA - 2022/09/09 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 4396
IS - 18
VL - 14
PMID - 36139555
SN - 2072-6694
ER -
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@article{2022_Gaponova,
author = {Olga Patutina and Ekaterina Burakova and Valentin Vlassov and Svetlana Gaponova and Aleksandra V. Sen’kova and Innokenty A. Savin and А. В. Марков and Elena Shmendel and Michael Maslov and Д.А. Стеценко and М. А. Зенкова},
title = {Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy},
journal = {Cancers},
year = {2022},
volume = {14},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {sep},
url = {https://doi.org/10.3390%2Fcancers14184396},
number = {18},
pages = {4396},
doi = {10.3390/cancers14184396}
}
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Gaponova, Svetlana, et al. “Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy.” Cancers, vol. 14, no. 18, Sep. 2022, p. 4396. https://doi.org/10.3390%2Fcancers14184396.
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