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

异鼠李素及其衍生物通过调节癌症相关成纤维细胞破坏胰腺导管腺癌结缔组织形成的抗纤维化作用

• 批准号: 21K14789
• 负责人: Ganbold Munkhzul
• 金额: $ 2.83万
• 依托单位: National Institute of Advanced Industrial Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-12-19 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K14789/
• 关键词: isorhamnetin; CAFs; PDAC; cell metabolism; natural compound; pancreatic cancer; flavonoid; desmoplasia; CAF; remodeling; Isorhamnetin; quercetin derivative

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.

综上所述，我们的研究结果表明，异鼠李素损害人PDAC CAFs线粒体呼吸和糖酵解，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，这可能驱动CAF从炎性表型转变为肌纤维母细胞样表型，如通过ACTA 2基因表达的适度增加所观察到的，尽管其他myCAF标志物减少，这表明异鼠李素的一般有益作用，这可能有助于进一步研究靶向CAF代谢和CAF与肿瘤细胞之间交联的PDAC治疗。

项目成果

Isorhamnetin Inhibits Pancreatic Cancer-Associated Fibroblasts Growth

异鼠李素抑制胰腺癌相关成纤维细胞的生长

• 发表时间: 2022
• 作者: 渡邉研志;秋庸裕（監修：植田充美）;Munkhzul Ganbold
• 通讯作者: Munkhzul Ganbold