UNASSIGNED: Herein we have investigated whether ligands to FXR and GPBAR1 modulate LIF/LIFR pathway in PDAC cells and whether these receptors are expressed in human neoplastic tissues.
UNASSIGNED: The transcriptome analysis of a cohort of PDCA patients revealed that expression of LIF and LIFR is increased in the neoplastic tissue in comparison to paired non-neoplastic tissues. By in vitro assay we found that both primary and secondary bile acids exert a weak antagonistic effect on LIF/LIFR signaling. In contrast, BAR502 a non-bile acid steroidal dual FXR and GPBAR1 ligand, potently inhibits binding of LIF to LIFR with an IC50 of 3.8 µM.
UNASSIGNED: BAR502 reverses the pattern LIF-induced in a FXR and GPBAR1 independent manner, suggesting a potential role for BAR502 in the treatment of LIFR overexpressing-PDAC.
本文中,我们研究了FXR和GPBAR1的配体是否调节PDAC细胞中的LIF/LIFR途径以及这些受体是否在人肿瘤组织中表达。
■一组PDCA患者的转录组分析显示,与配对的非肿瘤组织相比,肿瘤组织中LIF和LIFR的表达增加。通过体外测定,我们发现初级和次级胆汁酸对LIF/LIFR信号传导都具有弱的拮抗作用。相比之下,BAR502一种非胆汁酸甾体双FXR和GPBAR1配体,有效抑制LIF与LIFR的结合,IC50为3.8µM。
■BAR502以FXR和GPBAR1独立的方式反转LIF诱导的模式,提示BAR502在LIFR过表达PDAC治疗中的潜在作用。