Глиобластома - это наиболее частая и агрессивная форма опухоли головного мозга [269]. На сегодняшний день лечение глиобластомы носит скорее паллиативный характер и продлевает жизнь больного максимум на 2 года [270]. Одним из наиболее эффективных способов лечения глиобластомы является лучевая терапия, применение которой ограничено повреждающим действием на нормальные ткани. Соединения, способные усиливать гибель опухолевых клеток, предохраняя при этом нормальные ткани, представляют собой одно из наиболее актуальных направлений исследований.
С помощью колониеформирующего метода было продемонстрировано, что предварительная инкубация клеток глиобластомы с карнозином приводит к снижению выживаемости клеток после действия ионизирующего излучения по сравнению с контролем (Рис. 3.4.1). Ранее было показано, что обработка нормальных клеток карнозином снижает последствия повреждающего действия радиации. Введение мышам карнозина в течение нескольких дней перед облучением способствовало повышению выживаемости животных и сопровождалось увеличением эффективности образования селезеночных колоний гематопоэтическими стволовыми клетками из костного мозга облученных животных [218-220]. Кроме того, карнозин снижал степень повреждения плазмиды ДНК и количество разрывов в цепи ДНК, индуцированные действием ионизирующего излучения [271]. Исходя из полученных нами данных мы предполагаем, что карнозин способен избирательно снижать выживаемость опухолевых клеток под действием ионизирующего излучения, защищая при этом нормальные клетки. Полученные нами данные могут быть использованы на практике для разработки протоколов применения карнозина в терапии опухолей головного мозга.
ВЫВОДЫ
1. Исследован характер воздействия карнозина на пролиферацию культур опухолевых клеток: феохромоцитомы крысы (РС-12), карциномы горла и рта (FaDu и Cal27), карциномы молочной железы (MB231) и глиобластомы человека (U-118-MG). Обнаружено, что карнозин ингибирует пролиферацию всех исследованных клеточных линий. Наиболее выраженный эффект проявлялся на клетках глиобластомы человека U-118-MG;
2. Изучено влияние карнозина на уровень АФК и активность антиоксидантных ферментов глиобластомы. Выявлено, что ингибирование пролиферации клеток глиобластомы под действием карнозина сопровождается снижением уровня АФК и увеличением активности MnСОД;
3. Исследовано воздействие карнозина на клеточный цикл клеток РС-12 и U-118-MG. Установлено, что изменения в антиоксидантной системе сопровождаются накоплением клеток в G2 фазе клеточного цикла и усилением экспрессии циклина В1;
4. Проведено сравнение антипролиферативного эффекта карнозина с действием его производных и синтетического трипептида пинеалона. Выявлено, что метилированное производное карнозина, анзерин, ингибирует пролиферацию клеток опухолевых клеток эффективнее, чем карнозин;
5. Исследован эффект совместного применения карнозина и ионизирующего излучения на гибель опухолевых клеток. Обнаружено, что предварительная инкубация клеток с карнозином снижает выживаемость клеток глиобластомы под действием ионизирующего излучения.
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