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Activation of alpha‐smooth muscle actin‐positive myofibroblast‐like cells after chemotherapy with gemcitabine in a rat orthotopic pancreatic cancer model
Author(s) -
Yamao Jun,
Toyokawa Hideyoshi,
Kim Songtae,
Yamaki So,
Satoi Sohei,
Yanagimoto Hiroaki,
Yamamoto Tomohisa,
Hirooka Satoshi,
Matsui Yoichi,
Kwon AHon
Publication year - 2013
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1007/s00534-012-0576-9
Subject(s) - pancreatic cancer , gemcitabine , myofibroblast , hepatic stellate cell , cancer research , medicine , cancer , pancreatic tumor , pathology , ca19 9 , vascular smooth muscle , fibrosis , smooth muscle
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.