Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • 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
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Blood Cancer Discovery
    • 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
  • My Cart

Search

  • Advanced search
Cancer Prevention Research
Cancer Prevention Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
Chemoprevention and Biological Therapies

Abstract PR05: Low dose aspirin that reduces mortality from lung adenocarcinoma inhibits both platelet COX-1 and the biosynthesis of PGE2

John Oates, Pierre Massion, Bjorn Knollmann, James Smith, Elias Haddad, Philip Lammers, Denise Oram, Taneem Amin, Bradford Harris, Megan Hoeksema and Hyun Hwang
John Oates
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pierre Massion
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bjorn Knollmann
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Smith
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elias Haddad
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip Lammers
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Denise Oram
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Taneem Amin
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bradford Harris
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Megan Hoeksema
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyun Hwang
Vanderbilt University, Nashville, TN.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1940-6215.PREV-14-PR05 Published October 2015
  • Article
  • Info & Metrics
Loading
Abstracts: Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; September 27 - October 1, 2014; New Orleans, LA

Abstract

Background: Meta-analysis of the trials evaluating the effect of aspirin on cardiovascular outcomes demonstrated that aspirin prevented mortality from adenocarcinomas by 47% and reduced metastasis by 46%. Equivalent benefit was seen with both high and low doses of aspirin. We hypothesize that low dose aspirin blocks metastasis by inhibiting platelet COX-1 and also by inhibiting the biosynthesis of the pro-metastatic PGE2.

Methods and Results: The effect of a range of doses of aspirin on PGE2 biosynthesis in three lung adenocarcinoma cell lines was compared with that in washed platelets. PGE2 was measured by GC/MS. In the cancer cell lines, aspirin inhibits COX-2-dependent PGE2 production with IC50s equivalent to or less than that for platelet COX-1. The IC50s were: Platelet = 19.8 ± 1.5 μM; H2122 = 19.5 ± 5 μM; HCC827 = 3.9 ± 2 μM; A549 = 1.6 ± 0.4 μM.

To explore the extra-platelet effects of low dose aspirin in vivo, we examined the effect of aspirin 81 mg daily for 2 weeks on the biosynthesis of PGE2 and prostacyclin as reflected by their respective urinary metabolites in 54 healthy humans. The PGE2 metabolite was measured by LC/MS/MS and the prostacyclin metabolite by GC/MS. This dose of aspirin inhibited PGE2 production by 45% (p < 0.0001) and reduced prostacyclin by 37% (p < 0.0001).

Adherence of platelets to tumor cells facilitates metastasis. We determined the effect of adherence of ADP-activated washed platelets to lung adenocarcinoma cells (A549) on the PGE2 biosynthetic pathway. COX-2 expression was determined by Western blot, and cytosolic calcium by Fura-2 AM. Activated platelets increased cytosolic calcium in A549 cells by 22% (p < 0.001), increased expression of COX-2 by 8.6 fold (p<0.0001) and increased PGE2 biosynthesis by 8.1 fold (p < 0.0001), indicating that PGE2 production by tumor cells is enhanced by activated platelets.

Conclusion: These findings form the basis for a hypothesis that the remarkable effect of low dose aspirin on adenocarcinoma prevention and reduction in metastatic behavior could result from inhibition of platelet activation in concert with inhibition of platelet-induced PGE2 biosynthesis and direct inhibition of the catalytic activity COX-2 in circulating tumor cells.

Work funded by the Thoracic Program of the Vanderbilt Ingram Cancer Center

Citation Format: John Oates, Pierre Massion, Bjorn Knollmann, James Smith, Elias Haddad, Philip Lammers, Denise Oram, Taneem Amin, Bradford Harris, Megan Hoeksema, Hyun Hwang. Low dose aspirin that reduces mortality from lung adenocarcinoma inhibits both platelet COX-1 and the biosynthesis of PGE2. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR05.

  • ©2015 American Association for Cancer Research.
Previous
Back to top
Cancer Prevention Research: 8 (10 Supplement)
October 2015
Volume 8, Issue 10 Supplement
  • Table of Contents

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Prevention 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.
Abstract PR05: Low dose aspirin that reduces mortality from lung adenocarcinoma inhibits both platelet COX-1 and the biosynthesis of PGE2
(Your Name) has forwarded a page to you from Cancer Prevention Research
(Your Name) thought you would be interested in this article in Cancer Prevention Research.
Citation Tools
Abstract PR05: Low dose aspirin that reduces mortality from lung adenocarcinoma inhibits both platelet COX-1 and the biosynthesis of PGE2
John Oates, Pierre Massion, Bjorn Knollmann, James Smith, Elias Haddad, Philip Lammers, Denise Oram, Taneem Amin, Bradford Harris, Megan Hoeksema and Hyun Hwang
Cancer Prev Res October 1 2015 (8) (10 Supplement) PR05; DOI: 10.1158/1940-6215.PREV-14-PR05

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract PR05: Low dose aspirin that reduces mortality from lung adenocarcinoma inhibits both platelet COX-1 and the biosynthesis of PGE2
John Oates, Pierre Massion, Bjorn Knollmann, James Smith, Elias Haddad, Philip Lammers, Denise Oram, Taneem Amin, Bradford Harris, Megan Hoeksema and Hyun Hwang
Cancer Prev Res October 1 2015 (8) (10 Supplement) PR05; DOI: 10.1158/1940-6215.PREV-14-PR05
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
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Chemoprevention and Biological Therapies

  • Abstract PR09: Intermittent dosing regimens maintain efficacy of several cancer preventing drugs
  • Abstract PR03: Targeting multiple cell cycle regulatory points for the prevention of triple-negative breast cancer
Show more Chemoprevention and Biological Therapies

Spotlight on Proffered Abstracts: Oral Presentations - Proffered Abstracts

  • Abstract PR05: Low dose aspirin that reduces mortality from lung adenocarcinoma inhibits both platelet COX-1 and the biosynthesis of PGE2
Show more Spotlight on Proffered Abstracts: Oral Presentations - Proffered Abstracts
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Prevention Research

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

Copyright © 2019 by the American Association for Cancer Research.

Cancer Prevention Research
eISSN: 1940-6215
ISSN: 1940-6207

Advertisement