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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

  • Original article
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Journal of Hepato-Biliary-Pancreatic Sciences

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.

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Authors and Affiliations

  1. Department of Surgery, Kansai Medical University, 2-3-1 Shin-machi, Hirakata, Osaka, 573-1191, Japan

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

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  1. Jun Yamao
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  2. Hideyoshi Toyokawa
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  3. Songtae Kim
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  4. So Yamaki
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  5. Sohei Satoi
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  6. Hiroaki Yanagimoto
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  7. Tomohisa Yamamoto
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  8. Satoshi Hirooka
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  9. Yoichi Matsui
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Correspondence to Sohei Satoi.

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Yamao, J., Toyokawa, H., Kim, S. et al. Activation of alpha-smooth muscle actin-positive myofibroblast-like cells after chemotherapy with gemcitabine in a rat orthotopic pancreatic cancer model. J Hepatobiliary Pancreat Sci 20, 206–213 (2013). https://doi.org/10.1007/s00534-012-0576-9

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  • DOI: https://doi.org/10.1007/s00534-012-0576-9

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