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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number744
JournalOncology Letters
Volume22
Issue number4
DOIs
Publication statusPublished - Aug 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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