Original article

Journal of Hepato-Biliary-Pancreatic Sciences

, Volume 20, Issue 2, pp 206-213

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

  • Jun YamaoAffiliated withDepartment of Surgery, Kansai Medical University
  • , Hideyoshi ToyokawaAffiliated withDepartment of Surgery, Kansai Medical University
  • , Songtae KimAffiliated withDepartment of Surgery, Kansai Medical University
  • , So YamakiAffiliated withDepartment of Surgery, Kansai Medical University
  • , Sohei SatoiAffiliated withDepartment of Surgery, Kansai Medical University Email author 
  • , Hiroaki YanagimotoAffiliated withDepartment of Surgery, Kansai Medical University
  • , Tomohisa YamamotoAffiliated withDepartment of Surgery, Kansai Medical University
  • , Satoshi HirookaAffiliated withDepartment of Surgery, Kansai Medical University
  • , Yoichi MatsuiAffiliated withDepartment of Surgery, Kansai Medical University
    • , A-Hon KwonAffiliated withDepartment of Surgery, Kansai Medical University

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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