Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Research Article

Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells

Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Lin Cui, Kazuhiro Mizumoto and Masao Tanaka
Shingo Kozono
Departments of Surgery and Oncology, Kyushu University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenoki Ohuchida
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kenoki@surg1.med.kyushu-u.ac.jp
Daiki Eguchi
Graduate School of Medical Sciences, Kyushu University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Naoki Ikenaga
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Fujiwara
Graduate School of Medical Sciences, Kyushu University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lin Cui
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhiro Mizumoto
Department of Surgery and Oncology, Kyushu University Graduate School of Medical Sciences
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masao Tanaka
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/0008-5472.CAN-12-3180
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Pancreatic stellate cells (PSCs), which are implicated in desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress desmoplasia and exert anti-tumor effects against pancreatic cancer. Primary PSCs were established from pancreatic cancer tissue obtained during surgery. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of PSCs in a dose-dependent manner. Although supernatants of untreated PSCs increased the proliferation, invasiveness, and migration of pancreatic cancer cells (PCCs), supernatants of pirfenidone-treated PSCs decreased these effects. Exposure to PCC supernatant increased the production of platelet-derived growth factor-A, hepatic growth factor, collagen type I, fibronectin, and periostin in PSCs, which was significantly reduced by pirfenidone. Mice were subcutaneously implanted with PCCs (SUIT-2 cells) and PSCs into the right flank and PCCs alone into the left flank. Oral administration of pirfenidone to these mice significantly reduced tumor growth of co-implanted PCCs and PSCs, but not of PCCs alone. Pirfenidone also decreased the proliferation of PSCs and the deposition of collagen type I and periostin in tumors. In mice with orthotopic tumors consisting of PCCs co-implanted with PSCs, pirfenidone suppressed tumor growth, reduced the number of peritoneal disseminated nodules, and reduced the incidence of liver metastasis. Pirfenidone in combination with gemcitabine more effectively suppressed orthotopic tumor growth compared with pirfenidone or gemcitabine alone. In conclusion, our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of desmoplasia through regulating PSCs.

  • Received August 13, 2012.
  • Revision received January 10, 2013.
  • Accepted January 12, 2013.
  • Copyright © 2013, American Association for Cancer Research.
Next
Back to top

Published OnlineFirst January 24, 2013
doi: 10.1158/0008-5472.CAN-12-3180

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells
Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Lin Cui, Kazuhiro Mizumoto and Masao Tanaka
Cancer Res January 24 2013 DOI: 10.1158/0008-5472.CAN-12-3180

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells
Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Lin Cui, Kazuhiro Mizumoto and Masao Tanaka
Cancer Res January 24 2013 DOI: 10.1158/0008-5472.CAN-12-3180
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • MDA-9 mediates prostate cancer invasion
  • Targeting of MDSC increases efficiency of VEGFR-2 inhibitors
  • Enhancer remodeling in acquired resistance to ALK inhibitor
Show more Research Article
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement