Активация аутофагии в клетках рака молочной железы in vitro после воздействия ингибиторами PI3K/AKT/mTOR

Введение. Химиотерапия рака молочной железы имеет широкий спектр недостатков, в частности развитие сопутствующих инфекций и гормональных нарушений. Комбинация с синтетическими глюкокортикоидами позволяет расширить терапевтический интервал и снизить общую токсичность препаратов основной линии терапии. Однако длительное применение глюкокортикоидов способствует развитию ряда побочных эффектов, которые могут реализовываться за счет различных молекулярных механизмов. Так, глюкокортикоиды могут инициировать индукцию аутофагии, ведущую к выживанию опухолевых клеток. Запуск механизма аутофагии является mTOR-зависимым, в связи с чем актуальной является оценка возможности введения в качестве адъювантов в терапию рака молочной железы ингибиторов сигнального пути PI3K (фосфоинозитид-3‑киназа) / Akt (протеинкиназа B) / mTOR (мишень рапамицина млекопитающих).
Цель работы – анализ действия ингибиторов PI3K / Akt / mTOR рапамицина, вортманнина и LY-294002 в комбинации с глюкокортикоидами на запуск аутофагии в клеточных линиях рака молочной железы различного гистогенеза.
Материалы и методы. Методом Вестерн-блоттинга было показано, что рапамицин, вортманнин и LY-294002 ингибируют активность сигнального пути PI3K / Akt / mTOR и индуцируют аутофагию в клетках рака молочной железы, о чем судили по повышению уровня ключевого белка макроаутофагии, Beclin-1, и его фосфорилированных форм phospho-Beclin-1 по остаткам серина Ser93 и Ser30.
Заключение. В ходе работы было показано, что ингибиторы сигнального пути PI3K / Akt / mTOR в комбинации с дексаметазоном кооперативно подавляют сигнальный путь mTOR и активируют аутофагию в клетках РМЖ in vitro.

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