Effect of apolipoprotein A-I complexes with cytostatic drugs induce apoptosis in Ehrlich ascites carcinoma cell culture

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Abstract

Introduction. Improving the effectiveness of cancer treatment remains an urgent task today. The use of various transport forms for therapeutic agents makes it possible to improve their bioavailability and specificity of distribution in the body, reducing toxic effects.

Aim. This study aimed at evaluating the effect of complexes of the native protein apolipoprotein A-I with cytostatic drugs of various concentrations [0.1 and 1 mkg/ml] on the activation of caspase 3/7 in Ehrlich ascites carcinoma cell culture.

Materials and methods. ApoA-I was isolated from the HDL fraction of human blood plasma. The protein was conjugated with cytostatic drugs (actinomycin D, doxorubicin, vinblastine, melphalan). The experiments were carried out on cell culture of Ehrlich's ascites carcinoma. Incubation of Ehrlich ascites carcinoma cells with the studied complexes in various dosages was carried out for 24 hours, 30 minutes before the end the reagent CellEventTM Caspase-3/7 Green Detection Reagent (Thermo Fisher Scientific, USA) was added. The calculation of the number of apoptotic cells was recorded using the Program AxioVizion V.4.5.

Results. It has been shown that the addition of ApoA-I complexes with antitumor drugs promotes the activation of caspases 3/7 in Ehrlich ascites carcinoma cells when using cytostatic drugs in minimal concentrations [0.1 µg/ml]. Drugs without a carrier did not cause this effect.

Conclusion. The use of ApoA-I as a transport form of antitumor drugs contributes to a more effective activation of apoptosis in cells of Ehrlich ascites carcinoma in relation to cytostatics without a carrier.

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About the authors

N. V. Trifonova

Federal Research Center for Fundamental and Translational Medicine

Author for correspondence.
Email: Nataliya.V.T@yandex.ru
ORCID iD: 0000-0003-0697-8846

Junior Research Scientist, Laboratory of Medical Biotechnology; Research Institute of Biochemistry

Russian Federation, 2 Timakova Str., Novosibirsk, 630060

R. A. Knyazev

Federal Research Center for Fundamental and Translational Medicine

Email: knjazev_roman@mail.ru
ORCID iD: 0000-0003-2678-8783
SPIN-code: 7401-5637

Ph.D. (Biol.), Leading Research Scientist, Laboratory of Medical Biotechnology; Research Institute of Biochemistry

Russian Federation, 2 Timakova Str., Novosibirsk, 630060

M. V. Kotova

Federal Research Center for Fundamental and Translational Medicine

Email: zerokiri@mail.ru
ORCID iD: 0000-0001-6276-9630
SPIN-code: 3958-1142

Junior Research Scientist, Laboratory of Medical Biotechnology; Research Institute of Biochemistry

Russian Federation, 2 Timakova Str., Novosibirsk, 630060

L. M. Polyakov

Federal Research Center for Fundamental and Translational Medicine

Email: polyakov47.lev@yandex.ru
ORCID iD: 0000-0001-5905-8969
SPIN-code: 4600-3258

Dr.Sc. (Med.), Professor, Head of the Laboratory of Medical Biotechnology; Research Institute of Biochemistry

Russian Federation, 2 Timakova Str., Novosibirsk, 630060

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2. Fig. 1. Assessment of the number of apoptotic cells in the culture of Ehrlich ascites carcinoma in the control group and with the addition of apoА-I (0,5 µg/ml) (magnitude ×200)

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3. Fig. 2. Assessment of caspases 3/7 activity with the addition of cytostatics at concentrations of 1 and 0.1 µg/ml (magnitude ×200)

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4. Fig. 3. Assessment of caspases 3/7 activity with the addition of cytostatics at concentrations of 0.1 µg/ml (magnitude ×200)

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