аутофагия

Терафтал (натриевая соль 4,5-октакарбоксифталоцианина кобальта) снижает чувствительность опухолевых клеток к антрациклиновым антибиотикам и митоксантрону in vitro

ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ , , , , , ,

Т.А. Сидорова1, О.О. Рябая1, В.В. Татарский1, Д.А. Хоченков1, Е.С. Иванова1, О.Л. Калия2

1 ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

2 ФГУП ГНЦ «НИОПИК», ул. Б. Садовая, д. 1, корп. 4, Москва, Российская Федерация, 123995

Для переписки: Татьяна Александровна Сидорова, канд. мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; e-mail: tatsid@yahoo.com

Для цитирования: Сидорова Т.А., Рябая О.О., Татарский В.В. и др. Терафтал (натриевая соль 4,5-октакарбоксифталоцианина кобальта) снижает чувствительность опухолевых клеток к антрациклиновым антибиотикам и митоксантрону in vitro. Клиническая онкогематология. 2018;11(1):10–25.

DOI: 10.21320/2500-2139-2018-11-1-10-25

РЕФЕРАТ

Обоснование. Антрациклиновые антибиотики (АА) широко используются в клинической онкогематологии. Известно, что цитотоксичность АА снижается в присутствии гемина (FePPIX), эндогенного металлопорфирина.

Цель. Выяснить влияние терафтала (ТФ) и его структурного аналога FePPIX на степень цитотоксичности препаратов «антрахинонового» ряда — АА и митоксантрона (MiTOX) — in vitro.

Материалы и методы. В работе были использовались лейкозные клетки человека линии K562 и клетки аденокарциномы линии НСТ 116. Способность ТФ защищать опухолевые клетки от гибели, индуцированной АА, оценивали с помощью МТТ-метода, проточной цитометрии, световой микроскопии, цитохимического метода определения экспрессии b-галактозидазы с использованием в качестве субстрата X-Gal, ДНК-электрофореза, выхода ЛДГ, ОТ-ПЦР в реальном времени, радиометрического метода.

Результаты. По нашим данным, в присутствии ТФ (10 мкмоль/л) цитотоксичность АА и MiTOX снижается в среднем в 4 и 20 раз соответственно. Защитные свойства ТФ зависят от химической структуры АА. В присутствии ТФ токсичность акларубицина не меняется. В основе защиты ТФ/FePPIX от цитотоксичности АА может участвовать один и тот же механизм, который связан со снижением способности клеток, в т. ч. опухолевых при лейкозе, «накапливать» АА в присутствии модуляторов. ТФ/FePPIX «защищают» опухолевые клетки человека от гибели, индуцированной АА: апоптоза, некроза и преждевременного старения (АS). АS-сценарий, индуцированный в лейкозных клетках линии K562 комбинацией AA + ТФ/FePPIX, завершается появлением колоний суспензионных «маленьких» клеток. Вeclin-лизосомальный путь аутофагии не участвует в механизме снижения токсичности АА для клеток линии K562 в присутствии ТФ.

Заключение. Снижение цитотоксичности АА и возобновление роста популяции опухолевых клеток в присутствии ТФ и FePPIX следует учитывать при использовании гематопорфиринов и фталоцианинов, близких по структуре к ТФ, в качестве сенсибилизаторов в клинических протоколах.

Ключевые слова: антрациклиновые антибиотики, митоксантрон, терафтал, гемин, опухолевые клетки человека, препарат-индуцированное старение, аутофагия.

Получено: 2 июля 2017 г.

Принято в печать: 13 ноября 2017 г.

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Аутофагия: клеточная гибель или способ выживания?

ОБЗОРЫ , ,

О.В. Ковалева, М.С. Шитова, И.Б. Зборовская

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Взаимодействие процессов пролиферации, дифференцировки и гибели клеток служит неотъемлемой частью жизнедеятельности многоклеточных организмов. Нарушение баланса между этими процессами лежит в основе развития многих заболеваний человека. Понимание их молекулярных механизмов необходимо для поиска новых диагностических и терапевтических мишеней. В последнее десятилетие большой интерес у ученых вызывает процесс аутофагии и ее роль в жизнедеятельности клетки как в норме, так и при патологии. Аутофагия — это процесс утилизации клеточных органелл и макромолекул. Аутофагия сопровождает жизнедеятельность любой нормальной клетки в обычных условиях. Однако при определенных обстоятельствах аутофагия может приводить к клеточной гибели. Нарушения аутофагии играют роль в развитии онкологических, мышечных и нейродегенеративных заболеваний, кардиомиопатии и др.

Ключевые слова: апоптоз, аутофагия, канцерогенез

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