Concurrent inhibition of mTORC1 and mTORC2 by WYE-687 inhibits renal cell carcinoma cell growth in vitro and in vivo.
作者: Xiao-Dong PanDong-Hua GuJia-Hui MaoHua ZhuXinfeng ChenBing ZhengYuxi Shan
刊名: PLoS ONE, 2017, Vol.12 (3)
来源数据库: Directory of Open Access Journals
DOI: 10.1371/journal.pone.0172555
原始语种摘要: Mammalian target of rapamycin (mTOR)in renal cell carcinoma (RCC) represents a valuable oncotarget for treatment. We here tested the potential anti-RCC activity by a novel mTOR kinase inhibitor WYE-687in vitro and in vivo.WYE-687 was cytotoxic and anti-proliferative to established RCC cell lines (786-O and A498) and primary human RCC cells. Yet, it was non-cytotoxic toHK-2 tubular epithelial cells.WYE-687 provoked caspase-dependent apoptosis in the RCC cells. At the molecular level, WYE-687 almost completely blocked mTORC1 (p-S6K1 and p-S6) and mTORC2 (p-Akt Ser 473) activation in both 786-Ocells and primary human RCC cells, where it downregulated both hypoxia-inducible factor (HIF)-1α and HIF-2α expression. Significantly, oral administration of WYE-687 potently suppressed786-O tumor...
全文获取路径: DOAJ  (合作)
影响因子:3.73 (2012)

  • renal 肾的
  • carcinoma 癌症
  • inhibition 抑制
  • cytotoxic 细胞毒素的
  • growth 生长
  • RCC Readiness Condition Coder
  • cells 麻风细胞
  • preclinical 临证前期的
  • blocked 分块
  • activation 活化