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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 / Copyright

    Affiliations: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
    Copyright: © Sagara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 744
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    Published online on: August 20, 2021
       https://doi.org/10.3892/ol.2021.13005
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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