title: Activation of alpha-smooth muscle actin-positive myofibroblast-like cells after chemotherapy with gemcitabine in a rat orthotopic pancreatic cancer model.
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.
  
  
  CONCLUSIONS
  GEM may suppress not only the tumor cell proliferation but also suppress PSCs activation through VEGF reduction.
authors.affiliation: Department of Surgery, Kansai Medical University, 2-3-1 Shin-machi, Hirakata, Osaka 573-1191, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamao
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Toyokawa
authors.forename: Songtae
authors.initials: S
authors.lastname: Kim
authors.forename: So
authors.initials: S
authors.lastname: Yamaki
authors.forename: Sohei
authors.initials: S
authors.lastname: Satoi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirooka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsui
authors.forename: A-Hon
authors.initials: AH
authors.lastname: Kwon
mesh_terms: D000199:Actins / Q000096:biosynthesis* / Q000187:drug effects; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015153:Blotting, Western; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000187:drug effects; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000093542:Gemcitabine
chemical_list: D000199:Actins; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000093542:Gemcitabine; C498862:Acta2 protein, rat; C467498:vascular endothelial growth factor A, rat