British journal of pharmacology · 2013
The serine-threonine kinase p90RSK is a new target of enzastaurin in follicular lymphoma cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kheirallah S, Fruchon S, Ysebaert L, Blanc A, Capilla F, Marrot A, Alsaati T, Frenois F X, Benhadji K A, Fournié J J, Laurent G, Bezombes C
Аннотация
BACKGROUND AND PURPOSE: Follicular lymphoma is the second most common non-Hodgkin's lymphoma and, despite the introduction of rituximab for its treatment, this disease is still considered incurable. Besides genetic alterations involving Bcl-2, Bcl-6 or c-Myc, follicular lymphoma cells often display altered B-cell receptor signalling pathways including overactive PKC and PI3K/Akt systems.
EXPERIMENTAL APPROACH: The effect of enzastaurin, an inhibitor of PKC, was evaluated both in vitro on follicular lymphoma cell lines and in vivo on a xenograft murine model. Using pharmacological inhibitors and siRNA transfection, we determined the different signalling pathways after enzastaurin treatment.
KEY RESULTS: Enzastaurin inhibited the serine-threonine kinase p90RSK which has downstream effects on GSK3β. Bad and p70S6K. These signalling proteins control follicular lymphoma cell survival and apoptosis; which accounted for the inhibition by enzastaurin of cell survival and its induction of apoptosis of follicular lymphoma cell lines in vitro. Importantly, these results were replicated in vivo where enzastaurin inhibited the growth of follicular lymphoma xenografts in mice.
CONCLUSIONS AND IMPLICATIONS: The targeting of p90RSK by enzastaurin represents a new therapeutic option for the treatment of follicular lymphoma.
EXPERIMENTAL APPROACH: The effect of enzastaurin, an inhibitor of PKC, was evaluated both in vitro on follicular lymphoma cell lines and in vivo on a xenograft murine model. Using pharmacological inhibitors and siRNA transfection, we determined the different signalling pathways after enzastaurin treatment.
KEY RESULTS: Enzastaurin inhibited the serine-threonine kinase p90RSK which has downstream effects on GSK3β. Bad and p70S6K. These signalling proteins control follicular lymphoma cell survival and apoptosis; which accounted for the inhibition by enzastaurin of cell survival and its induction of apoptosis of follicular lymphoma cell lines in vitro. Importantly, these results were replicated in vivo where enzastaurin inhibited the growth of follicular lymphoma xenografts in mice.
CONCLUSIONS AND IMPLICATIONS: The targeting of p90RSK by enzastaurin represents a new therapeutic option for the treatment of follicular lymphoma.
Предметные рубрики MeSH
AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell SurvivalDose-Response Relationship, DrugGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaLymphoma, FollicularMiceMice, SCIDMolecular Targeted TherapyPhosphorylationProtein Kinase InhibitorsRNA InterferenceRibosomal Protein S6 Kinases, 70-kDaRibosomal Protein S6 Kinases, 90-kDaSignal TransductionTime FactorsTransfectionTumor BurdenXenograft Model Antitumor Assaysbcl-Associated Death Protein