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

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• 作者：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)
  
• 关键词：Pancreatic cancer ; Alpha ; smooth muscle actin ; Myofibroblast ; like cell ; Chemotherapy ; Vascular endothelial growth factor
• 刊名：Journal of Hepato-Biliary-Pancreatic Sciences
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：20
• 期：2
• 页码：206-213
• 全文大小：647KB
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• 作者单位：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. Department of Surgery, Kansai Medical University, 2-3-1 Shin-machi, Hirakata, Osaka, 573-1191, Japan
  

文摘

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.