Journal of Hepato-Biliary-Pancreatic Sciences

, Volume 20, Issue 2, pp 206–213 | Cite as

Activation of alpha-smooth muscle actin-positive myofibroblast-like cells after chemotherapy with gemcitabine in a rat orthotopic pancreatic cancer model

  • Jun Yamao
  • Hideyoshi Toyokawa
  • Songtae Kim
  • So Yamaki
  • Sohei Satoi
  • Hiroaki Yanagimoto
  • Tomohisa Yamamoto
  • Satoshi Hirooka
  • Yoichi Matsui
  • A-Hon Kwon
Original article

Abstract

Background

To investigate the behavior of activated pancreatic stellate cells (PSCs), which express alpha-smooth muscle actin (α-SMA), and pancreatic cancer cells in vivo, we examined the expression of α-SMA-positive myofibroblast-like cells in pancreatic cancer tissue after treatment with gemcitabine (GEM) using a Lewis orthotopic rat pancreatic cancer model.

Methods

The effect of GEM on DSL-6A/C1 cell proliferation was determined by cell counting method. The orthotopic pancreatic cancer animals were prepared with DSL-6A/C cells, and treated with GEM (100 mg/kg/weekly, for 3 weeks). At the end of treatment, α-SMA expression, fibrosis, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) were evaluated by histopathological and Western blot analyses.

Results

DSL-6A/C1 cell proliferation was significantly reduced by co-culturing with GEM in vitro. Survival time of pancreatic cancer animals (59.6 ± 13.4 days) was significantly improved by treatment with GEM (89.6 ± 21.8 days; p = 0.0005). Alpha-SMA expression in pancreatic cancer tissue was significantly reduced after treatment with GEM (p = 0.03), however, there was no significant difference in Sirius-red expression. Expression of VEGF was significantly reduced by GEM treatment, but the expression of TGF-β1 was not inhibited.

Conclusion

GEM may suppress not only the tumor cell proliferation but also suppress PSCs activation through VEGF reduction.

Keywords

Pancreatic cancer Alpha-smooth muscle actin Myofibroblast-like cell Chemotherapy Vascular endothelial growth factor 

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Copyright information

© Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer Japan 2012

Authors and Affiliations

  • Jun Yamao
    • 1
  • Hideyoshi Toyokawa
    • 1
  • Songtae Kim
    • 1
  • So Yamaki
    • 1
  • Sohei Satoi
    • 1
  • Hiroaki Yanagimoto
    • 1
  • Tomohisa Yamamoto
    • 1
  • Satoshi Hirooka
    • 1
  • Yoichi Matsui
    • 1
  • A-Hon Kwon
    • 1
  1. 1.Department of SurgeryKansai Medical UniversityHirakataJapan

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