antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2023-68-7-8-53-61antibiotics-1063Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ И ПРАКТИКАCLINICAL RESEARCH AND PRACTICEОценка синергетического эффекта комбинации доксорубицина и вориностата в отношении опухолевых клеток молочной железы с помощью модели LoeweEvaluation of the Synergistic Effect of the Combination of Doxorubicin and Vorinostat on Breast Tumor Cells Using the Loewe Modelhttps://orcid.org/0000-0002-9999-4652МоллаеваМ. Р.MollaevaМ. R.

Моллаева Мария Романовна — младший научный сотрудник

Москва

Scopus Author ID: 57201648257

Mariia R. Mollaeva — junior researcher

Moscow

Scopus Author ID: 57201648257

https://orcid.org/0000-0003-3361-9136ЯббаровН. Г.YabbarovN. G.

Яббаров Никита Григорьевич — к. б. н., старший научный сотрудник

Москва

Scopus Author ID: 50462552500

Nikita G. Yabbarov — Ph. D. in Biology, senior researcher

Moscow

Scopus Author ID: 50462552500

https://orcid.org/0000-0002-1976-1972СоколМ. Б.SokolМ. В.

Сокол Мария Борисовна — младший научный сотрудник

Москва

Scopus Author ID: 57195755669

 

Mariya B. Sokol — junior researcher

Moscow

Scopus Author ID: 57195755669

 

https://orcid.org/0000-0001-6061-4803ЧиркинаМ. В.ChirkinaМ. V.

Чиркина Маргарита Викторовна — младший научный сотрудник

Москва

Scopus Author ID: 57196439676

 

Margarita V. Chirkina — junior researcher

Moscow

Scopus Author ID: 57196439676

 

https://orcid.org/0000-0002-1931-3117НикольскаяЕ. Д.NikolskayaE. D.

Никольская Елена Дмитриевна — к. х. н., старший научный сотрудник

Москва

Scopus Author ID: 57189605012

 

Elena D. Nikolskaya — Ph. D. in Chemistry, senior researcher

Moscow

Scopus Author ID: 57189605012

Институт биохимической физики им. Н. М. Эмануэля РАНРоссияEmanuel Institute of Biochemical Physics of the RAS (IBCP RAS)Russian Federation202325122023687-85361Copyright © ООО «Издательство ОКИ», 20232023ООО «Издательство ОКИ»ООО «Издательство ОКИ»https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNoticehttps://www.antibiotics-chemotherapy.ru/jour/article/view/1063

Комбинация двух или более лекарственных средств находит всё большее применение при разработке новых схем лечения различных заболеваний. Так, использование комбинаций ингибиторов гистон деацетилаз с традиционными препаратами для лечения солидных злокачественных новообразований является актуальным направлением. Данное исследование посвящено поиску эффективного соотношения вориностата (SAHA) и доксорубицина (DOX) для терапии различных подтипов опухоли молочной железы. С помощью МТТ-теста оценили выживаемость клеток линий HCC-1954, SKBR-3, MCF-7, MCF-7/ADR, MDA-MB-231 в условиях инкубации с 64 вариантами концентрационных комбинаций SAHA и DOX, что позволило определить эффект взаимодействий комбинаций SAHA/DOX (антагонистический, аддитивный, синергетический). Провели расчёт индекса синергизма SAHA/DOX с помощью математической модели Loewe. Эффект соотношений SAHA/DOX, обладающих наибольшим индексом синергизма в отношении каждой линии опухолевых клеток, подтверждали с помощью метода Чоу–Талалай. Было показано, что наибольший синергизм комбинация SAHA/DOX проявляла в отношении клеток линий HCC-1954, MCF-7/ADR и SKBR-3, относящихся к HER2-позитивному подтипу. Среднее значение соотношений SAHA/DOX, обладающих наибольшим синергизмом в отношении опухолевых клеток, составило 30:1 (SAHA к DOX, соответственно). Способность выявленной комбинации эффективно стимулировать апоптоз была подтверждена на наиболее чувствительных к SAHA/DOX терапии клетках линии HCC-1954. Таким образом, модель Loewe позволила выявить комбинацию препаратов, обладающую синергетическим эффектом, что подтверждалось методом Чоу–Талалай, а полученные данные свидетельствуют о перспективности использования комбинации SAHA/DOX (30:1) в лечении HER2-позитивного подтипа опухолей молочной железы.

The combination of two or more medications is increasingly more common in the development of new treatment guidelines for common diseases. Thus, the use of combinations of histone deacetylase inhibitors with chemotherapeutic agents is a current trend in solid tumor treatment. The aim of this study was to investigate an effective vorinostat (SAHA) to doxorubicin (DOX) ratio for the treatment of different subtypes of breast cancer. The survival of HCC-1954, SKBR-3, MCF-7, MCF-7/ADR, MDA-MB-231 cell lines was assessed under incubation conditions with 64 variants of SAHA and DOX combinations using the MTT assay. This made it possible to determine the effect of interactions of SAHA/DOX combinations (antagonistic, additive, synergistic), as well as calculate the SAHA/DOX synergy index using the Loewe additivity model. The effect of SAHA/DOX ratios with the highest synergistic index for each tumor cell line was confirmed using the Chou-Talalay method. It was shown that the SAHA/DOX combination exhibited the greatest synergism in relation to HCC-1954, MCF-7/ADR and SKBR-3 cell lines belonging to the HER2-positive subtype. The average value of SAHA/DOX ratio with the highest synergy against breast cancer cells was 30:1 (SAHA to DOX, respectively). The ability of SAHA/DOX combination to effectively trigger apoptosis was confirmed in the most sensitive to SAHA/DOX therapy HCC-1954 cells. Thus, the Loewe model made it possible to identify the drug combination with the highest synergistic anticancer effect, which was confirmed using Chou-Talalay method. The data obtained demonstrates great potential of SAHA/DOX combination (30:1) for the treatment of HER2-positive breast cancer.

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The authors declare that there are no conflicts of interest present.