PDF(Pubmed)
Abstract：
Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients.
摘要：
肌肉浸润性膀胱癌（BC）可分为2个主要亚组-基底/鳞状（BASQ）肿瘤和管腔肿瘤。由于Pparg在BASQ肿瘤中表达低或检测不到，我们测试了罗格列酮的作用,PPARG激动剂,在BASQBC的小鼠模型中。我们发现罗格列酮减少增殖，而罗格列酮加曲美替尼治疗，MEK抑制剂，诱导细胞凋亡，1个月后肿瘤体积减少91%。罗格列酮和曲美替尼也诱导肿瘤从BASQ向管腔分化转变，我们的分析表明是由类视黄醇信号介导的，已知驱动腔分化程序的途径。我们的数据表明罗格列酮,曲美替尼,和类维生素A，这些都是FDA批准的，在BASQ肿瘤患者中可能具有临床活性。
