Anti-fibrotic effect of isorhamnetin and its derivatives on disruption of pancreatic ductal adenocarcinoma desmoplasia by regulation of cancer-associated fibroblasts

综上所述，我们的研究结果表明，异鼠李素损伤了人PDAC CAF的线粒体呼吸和糖酵解，导致线粒体丢失，并导致细胞死亡和细胞周期停滞。特别是ICAF标志物被强烈抑制，这可能促使CAF从炎症性转化为肌成纤维细胞样表型，ACTA2基因表达适度增加，而其他myCAF标志物表达降低，提示异鼠李素具有普遍的有利作用，这可能有助于进一步研究针对CAFS代谢和CAF与肿瘤细胞之间的交联的PDAC治疗。

Taken together, our findings demonstrated that isorhamnetin impaired human PDAC CAFs mitochondrial respiration and glycolysis with mitochondrial loss and caused cell death and cell cycle arrest. In particular, iCAF markers were strongly inhibited which might drive CAFs to shift from inflammatory to myofibroblast-like phenotype as observed by the moderate increase in ACTA2 gene expression although other myCAFs markers were reduced, suggesting general benefic effects of isorhamnetin which could contribute for further investigation of PDAC therapy targeting CAFs metabolism and crosslink between CAFs and tumor cells.