顺铂
癌症研究
基因敲除
体内
细胞生长
化学
药理学
医学
细胞凋亡
生物
化疗
内科学
生物化学
生物技术
作者
Karin Schelch,Dominik Emminger,Benjamin Zitta,Thomas G. Johnson,Verena Kopatz,Sebastian K. Eder,Alexander Ries,Alessia Stefanelli,Petra Heffeter,Mir Alireza Hoda,Konrad Höetzenecker,Balázs Döme,Walter Berger,Glen Reid,Michael Grusch
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-10-01
卷期号:574: 216395-216395
被引量:3
标识
DOI:10.1016/j.canlet.2023.216395
摘要
Pleural mesothelioma (PM) is characterized by poor prognosis and limited therapeutic options. Y-box-binding protein 1 (YB-1) was shown to drive growth and migration of PM cells. Here, we evaluated the effect of genetic and pharmacological targeting of YB-1 on PM growth and response to cisplatin and radiation treatment. YB-1 knockdown via siRNA resulted in reduced PM cell growth, which significantly correlated with wt BAP1 and mutant NF2 and P53 status. Entinostat inhibited YB-1 deacetylation and its efficacy correlated with YB-1 knockdown-induced growth inhibition in 20 p.m. cell lines. Tumor growth inhibition by siRNA as well as entinostat was confirmed in mouse xenotransplant models. Furthermore, both YBX1-targeting siRNA and entinostat enhanced sensitivity to cisplatin and radiation. In particular, entinostat showed strong synergistic interactions with cisplatin which was linked to significantly increased cellular platinum uptake in all investigated cell models. Importantly, in a mouse model, the combination of cisplatin and entinostat also resulted in stronger growth inhibition than each treatment alone. Our study highlights YB-1 as an attractive target in PM and demonstrates that targeting YB-1 via entinostat is a promising approach to enhance cisplatin and radiation sensitivity.
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