Open Access

Repositioning of duloxetine to target pancreatic stellate cells

  • Authors:
    • Akiko Sagara
    • Kohei Nakata
    • Sokichi Matsumoto
    • Weiyu Guan
    • Tomohiko Shinkawa
    • Chika Iwamoto
    • Naoki Ikenaga
    • Kenoki Ohuchida
    • Masafumi Nakamura
  • View Affiliations

  • Published online on: August 20, 2021     https://doi.org/10.3892/ol.2021.13005
  • Article Number: 744
  • Copyright: © Sagara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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October-2021
Volume 22 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Sagara A, Nakata K, Matsumoto S, Guan W, Shinkawa T, Iwamoto C, Ikenaga N, Ohuchida K and Nakamura M: Repositioning of duloxetine to target pancreatic stellate cells. Oncol Lett 22: 744, 2021
APA
Sagara, A., Nakata, K., Matsumoto, S., Guan, W., Shinkawa, T., Iwamoto, C. ... Nakamura, M. (2021). Repositioning of duloxetine to target pancreatic stellate cells. Oncology Letters, 22, 744. https://doi.org/10.3892/ol.2021.13005
MLA
Sagara, A., Nakata, K., Matsumoto, S., Guan, W., Shinkawa, T., Iwamoto, C., Ikenaga, N., Ohuchida, K., Nakamura, M."Repositioning of duloxetine to target pancreatic stellate cells". Oncology Letters 22.4 (2021): 744.
Chicago
Sagara, A., Nakata, K., Matsumoto, S., Guan, W., Shinkawa, T., Iwamoto, C., Ikenaga, N., Ohuchida, K., Nakamura, M."Repositioning of duloxetine to target pancreatic stellate cells". Oncology Letters 22, no. 4 (2021): 744. https://doi.org/10.3892/ol.2021.13005