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Transport and toxicity of 5-fluorouracil, doxorubicin, and cyclophosphamide in in vitro placental barrier model based on BeWo b30 cells

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Abstract

An in vitro placental barrier model based on human choriocarcinoma BeWo b30 cell line was considered as a method of preclinical study of the transport and toxicity of antitumor agents and other organic compounds. Low permeabilities were found for 5-fluorouracil as an example of hydrophilic compound and for doxorubicin as an example of a lipophilic compound with a high degree of binding to proteins and DNA and a high permeability was found for cyclophosphamide as an example of lipophilic compound with a low degree of binding to proteins. Using impedance spectrometry and cell viability assessment via reduction of resazurin to resorufin, a pronounced cytotoxic effect of doxorubicin and good tolerance of 5-fluorouracil and cyclophosphamide by the cells were shown for drug concentrations equal to the maximum concentrations in the patients’ blood during the treatment of breast cancer.

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Correspondence to E. N. Knyazev.

Additional information

The study was carried out using the research equipment of the Center for Collective Use “Post-Genomic and Metabolomic Investigation Methods in Molecular Biology” based on the LLC Research and Development Center BioClinicum.

This work was financially supported by the Ministry of Science and Education of the Russian Federation (Federal Target Program “Research and Development along the Priority Trends of the Science and technology Sector of Russia for 2014–2020” (Project No. RFMEFI58817X0007)).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2344–2349, December, 2019.

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Knyazev, E.N., Nikulin, S.V., Khristichenko, A.Y. et al. Transport and toxicity of 5-fluorouracil, doxorubicin, and cyclophosphamide in in vitro placental barrier model based on BeWo b30 cells. Russ Chem Bull 68, 2344–2349 (2019). https://doi.org/10.1007/s11172-019-2709-7

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  • DOI: https://doi.org/10.1007/s11172-019-2709-7

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