Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press115610.17650/1726-9784-2019-18-2-51-59ORIGINAL REPORTSОРИГИНАЛЬНЫЕ СТАТЬИTeraphtal decreased the sensitivity tumor cells to doxorubicine in vitro but does not affect its antitumor effect in vivo .Терафтал снижает чувствительность опухолевых клеток к доксорубицину in vitro, но не влияет на его противоопухолевый эффект in vivo .https://orcid.org/0000-0003-3498-061XSidorovaT. A.СидороваТ. А.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

tatsid@yahoo.comhttps://orcid.org/0000-0001-6295-3497RyabayaO. O.РябаяО. О.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

Prokof’yevaA. A.ПрокофьеваА. А.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

TatarskiyV. V.ТатарскийВ. В.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

AndronovaN. A.АндроноваА. А.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

RomanenkoV. I.РоманенкоВ. И.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

https://orcid.org/0000-0002-5694-3492KhochenkovD. A.ХоченковД. А.
Russian Federation

24 Kashirskoe Sh., Moscow 115478.

115478 Москва, Каширское ш., 24.

N.N. Blokhin NMRCO Ministry of Health of Russia.ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава России.1506201918251591506201915062019https://bioterapevt.abvpress.ru/jour/article/view/1156

Introduction . Anthracycline antibiotic doxorubicin (DOX) is widely used in clinical oncology. It is known that hemin, endogenious compound, has the ability to modulate DOX cytotoxicity. We found that DOX toxicity against mammalian cancer cells can be decreased in vitro in the presence of teraftal (ТF), the component anticancer binaric catalytic system (TF + ascorbic acid).

Purpose . To study the influence of TF on anticancer effect of DOX.

Materials and methods . The mouse melanoma cell line B16 / F10 and mouse transplanted tumor B16 were used. The TF ability to protect from DOX-induced cell death were measured by MTT-assay, flow сytometry, light microscopy, cytochemical determination of ß-galactosidase expression, radiometric assay and tumor growth inhibition assay in vivo.

Results. The sensitivity of mouse melanoma cell line B16 / F10 to DOX decreased in the presence TF (10–20 mkM) in the mean by 4–6 fold. The same mechanism takes part into the decrease of DOX cytotoxicity at the presence of TF / hemin khown which connects with the cell ability to accumulate of drug. TF protect the mouse melanoma cells B16 / F10 from apoptosis, induced by DOX throwing switching on cell premature senescence programme. The antitumor effect of DOX against mouse transplanted melanoma B16 at presence of TF was the same as DOX alone.

Conclusions. The TF potency to decrease the sensitivity of cancer cells to DOX in vitro does not correlate with its ability to modulate аnthracycline antibiotics anticancer effect in vivo. 

Введение . Антрациклиновый антибиотик доксорубицин (DOX) широко используется в клинической онкологии. Известно, что гемин, эндогенный метаболит, обладает способностью модулировать цитотоксичность DOX. По нашим данным, токсичность DOX для опухолевых клеток млекопитающих, растущих in vitro, снижается в присутствии терафтала (ТФ, натриевая соль 4,5-октакарбоксифталоцианина кобальта), компонента бинарной каталитической системы (ТФ + аскорбиновая кислота).

Цель исследования – выяснить, влияет ли ТФ на противоопухолевый эффект DOX in vivo.

Материалы и методы. В работе были использованы опухолевые клетки меланомы мыши линии В16 / F10 и перевиваемая опухоль меланомы В16. Способность ТФ защищать опухолевые клетки от гибели, индуцированной DOX, оценивали с помощью МТТ-метода, проточной цитометрии, световой микроскопии, цитохимического метода определения экспрессии ß-галактозидазы, радиометрического метода. Противоопухолевый эффект препаратов в режимах (DOX ± ТФ) оценивался по продолжительности жизни животных.

Результаты. По нашим данным, токсичность DOX относительно клеток меланомы мышей линии В16 / F10 в присутствии ТФ (10–20 мкМ) снижается в среднем в 4–6 раз. ТФ защищает опухолевые клетки линии В16 / F10 от гибели путем апоптоза, индуцированного DOX, включая в клетке программу преждевременного старения. В защите ТФ / гемина от цитотоксичности DOX участвует один и тот же механизм, который связан со снижением способности клеток «накапливать» антрациклиновые антибиотики в присутствии модуляторов. Противоопухолевая активность DOX при лечении мышей с перевиваемой опухолью меланомы В16 в комбинации с ТФ не отличается от эффективности антрациклиновых антибиотиков в режиме монотерапии.

Заключение. Способность ТФ снижать цитотоксичность DOX для клеток меланомы мышей линии В16 / F10, наблюдаемая in vitro, не влияет на противоопухолевый эффект DOX в условиях комбинированного воздействия препаратов. 

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