|
ИСТИНА |
Войти в систему Регистрация |
Интеллектуальная Система Тематического Исследования НАукометрических данных |
||
Inhibition of Ephrin B3-mediated survival signalling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412статья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 7 декабря 2013 г.
- Авторы: Ståhl S., Kaminskyy V.O., Efazat G., Hyrslova Vaculova, Rodriguez-Nieto A., Moshfegh S., Lewensohn A., Viktorsson R., K, Zhivotovsky B.
- Журнал: Cell death & disease
- Том: 4
- Номер: 1
- Год издания: 2013
- Издательство: Nature Pub. Group
- Местоположение издательства: United Kingdom
- Первая страница: 454
- Последняя страница: 454
- DOI: 10.1038/cddis.2012.188
- Аннотация: Radiation therapy is frequently used to treat non-small cell lung cancers (NSCLCs). We have previously shown that a combination of ionizing radiation (IR) and the staurosporine analog PKC 412, but not Ro 31-8220, increases cell death in NSCLC cells. To identify genes involved in the enhancement of cell death, a total gene profiling in response to co-administration of (i) PKC 412 with IR, or (ii) Ro 31-8220 with IR was implemented. These combined treatments caused upregulation of 140 and 179 genes and downregulation of 253 and 425 genes, respectively. Certain genes were selected and verified by real-time quantitative PCR and, of these genes, robust suppression of Ephrin B3 expression was suggested as a possible cell death-inducing mechanism of combined treatment with IR and PKC 412. Indeed, silencing of Ephrin B3 using siRNA in NSCLC cells resulted in a major alteration of their morphology with an elongated phenotype, decreased proliferation and increased cell death signaling. Moreover, silencing of Ephrin B3 in combination with IR caused a decrease in IR-mediated G 2-arrest, induced cellular senescence, inhibited MAPK ERK and p38 phosphorylation, and caused an upregulation of p27kip1 expression. Finally, silencing of Ephrin B3 in combination with IR sensitized U-1810 cells to IR-induced apoptosis. In conclusion, we identify and describe Ephrin B3 as a putative signaling molecule involved in the response of NSCLC cells to combined treatment with PKC 412 and ionizing radiation. © 2013 Macmillan Publishers Limited All rights reserved.
- Добавил в систему: Животовский Борис Давидович