Repositioning of duloxetine to target pancreatic stellate cells

AKIKO SAGARA, KOHEI NAKATA, SOKICHI MATSUMOTO, WEIYU GUAN, TOMOHIKO SHINKAWA, CHIKA IWAMOTO, NAOKI IKENAGA, KENOKI OHUCHIDA, MASAFUMI NAKAMURA

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Pancreatic cancer cells (PCCs) are surrounded by an abundant stroma, which is produced by pancreatic stellate cells (PSCs). PSCs promote tumor cell proliferation and invasion. The objective of the current study was to identify compounds that suppress PSC activation. Gene expression profiles of cancer-derived fibroblasts and normal fibroblasts were used, and the pathway analysis suggested altered pathways that were chosen for validation. It was found that the 'neuroactive ligand-receptor interaction' pathway from the Kyoto Encyclopedia of Genes and Genomes pathway analysis was one of the altered pathways. Several compounds related with this pathway were chosen, and changes in PSC activity were investigated using fluorescence staining of lipid droplets, reverse transcription-quantitative PCR, western blotting, and invasion and migration assays. Among these candidates, duloxetine, a serotonin-noradrenaline reuptake inhibitor, was found to suppress PSC activation and disrupt tumor-stromal interaction. Thus, duloxetine may be a potential drug for suppressing PSC activation and pancreatic cancer growth.

本文言語英語
論文番号744
ジャーナルOncology Letters
22
4
DOI
出版ステータス出版済み - 8月 2021

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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