Antimetastatic Activity of Combined Topotecan and Tyrosyl-DNA Phosphodiesterase-1 Inhibitor on Modeled Lewis Lung Carcinoma
- Authors: Koldysheva E.V.1, Men’shchikova A.P.2, Lushnikova E.L.1, Popova N.A.3,2, Kaledin V.I.3, Nikolin V.P.3, Zakharenko A.L.4, Luzina O.A.5, Salakhutdinov N.F.5,2, Lavrik O.I.4,2
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Affiliations:
- Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
- Novosibirsk National Research State University
- Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences
- Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences
- N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Academy of Sciences
- Issue: Vol 166, No 5 (2019)
- Pages: 661-666
- Section: Article
- URL: https://journals.rcsi.science/0007-4888/article/view/241261
- DOI: https://doi.org/10.1007/s10517-019-04413-3
- ID: 241261
Cite item
Abstract
The antimetastatic activity of combined or individual administration of topotecan and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitor was examined under various administration schedules in mice with Lewis lung carcinoma modeled by intravenous injection of 200,000 clone/mouse. The greatest antimetastatic effect was observed after combined use of topotecan and Tdp1 inhibitor as documented by macroscopic study of the lungs that revealed the decreased metastatic scores by 76, 91, or 74% at the respective inhibitor doses of 2, 4, or 6 mg/mouse, respectively, in parallel with inhibition of metastasis up to 98% (at inhibitor dose of 4 mg/mouse) and morphological and morphometric analyses of the lung sections, which revealed elevation of metastasis growth delay index to 86 and 63% at the respective inhibitor doses of 4 and 6 mg/mouse, respectively. The combined administration of topotecan and Tdp1 inhibitor is viewed as the most effective way to eliminate the metastatic formations with possible restitution of focal lesions.
About the authors
E. V. Koldysheva
Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
Author for correspondence.
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
A. P. Men’shchikova
Novosibirsk National Research State University
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
E. L. Lushnikova
Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
N. A. Popova
Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences; Novosibirsk National Research State University
Email: pathol@inbox.ru
Russian Federation, Novosibirsk; Novosibirsk
V. I. Kaledin
Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
V. P. Nikolin
Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
A. L. Zakharenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
O. A. Luzina
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Academy of Sciences
Email: pathol@inbox.ru
Russian Federation, Novosibirsk
N. F. Salakhutdinov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Academy of Sciences; Novosibirsk National Research State University
Email: pathol@inbox.ru
Russian Federation, Novosibirsk; Novosibirsk
O. I. Lavrik
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences; Novosibirsk National Research State University
Email: pathol@inbox.ru
Russian Federation, Novosibirsk; Novosibirsk