Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Growth of Human Tumor Cells in Macroporous Microcarriers Results in p53-Independent, Decreased Cisplatin Sensitivity Relative to Monolayers

Barry J. Maurer, Michael A. Ihnat, Cindy Morgan, Janice Pullman, Craig O’Brien, Steven W. Johnson, Janet S. Rasey and Marilyn M. Cornwell
Molecular Pharmacology May 1999, 55 (5) 938-947;
Barry J. Maurer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael A. Ihnat
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cindy Morgan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janice Pullman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Craig O’Brien
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven W. Johnson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janet S. Rasey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marilyn M. Cornwell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Multicellular contact has been shown to influence the in vitro sensitivity of cells to drug treatment. We investigated the use of macroporous gelatin microcarriers, CultiSpher-G, as a convenient laboratory system for the molecular analysis of this “contact effect”. We determined that human A549 cells can be grown in CultiSphers with growth and cell cycle parameters similar to those of monolayers. In addition, cells in CultiSphers express less p27/kip1, an indicator of cell cycle arrest, than equivalent cells in monolayers. When treated with drugs, A549 cells grown in CultiSphers or monolayers accumulate equivalent amounts of platinum-DNA adducts and similar amounts of doxorubicin. Moreover, A549 and KB-3-1 cells in CultiSphers have significantly decreased sensitivity tocis-platinum(II)diammine dichloride (cisplatin), 4-hydroperoxycyclophosphamide, doxorubicin, and paclitaxel (taxol) compared with cells in monolayers when assayed by clonogenic survival. Cisplatin treatment in monolayers or CultiSphers did not result in apoptotic cell death. In contrast, paclitaxel caused a significant amount of sub-G1 DNA, an indicator of apoptosis, which was diminished when cells were grown in CultiSphers compared with monolayers. When grown in CultiSphers, cells with abrogated p53 function (A549/16E6 and NCI-H1299) were less sensitive to cisplatin than the corresponding monolayer cells, indicating that the decrease in sensitivity is p53 independent. Taken together, the data suggest that CultiSpher-G microcarriers are a useful in vitro system to examine the effects of three-dimensional cell contact on drug sensitivity of human tumor cells.

Footnotes

  • Send reprint requests to: Dr. Marilyn M. Cornwell, Fred Hutchinson Cancer Center, Mail Stop D2–100, 1100 Fairview Ave. N., Seattle, WA 98109. E-mail: mcornwel{at}fhcrc.org

  • ↵1 These authors contributed equally to this manuscript.

  • ↵2 Current address: Childrens Center for Cancer and Blood Diseases, Childrens Hospital Los Angeles Research Institute, MS 57, 4650 Sunset Blvd., Los Angeles, CA 90027.

  • This work was supported by Public Health Service Grant RO1 CA63419 (to M.M. Cornwell). J. Rasey was supported by National Institutes of Health (NIH) Grant R37 CA34570. B. Maurer was supported by NIH training Grant T32 CA 09351. M. Ihnat was supported by NIH training Grant T32 DK07742–02 through the University of Washington School of Medicine, Department of Gastroenterology.

  • Abbreviations:
    4-HC
    4-hydroperoxycyclophosphamide
    cisplatin
    cis-platinum(II)diammine dichloride
    Pt-DNA
    platinum-DNA
    TBST
    10 mM Tris-HCl, pH 8, 150 mM NaCl, 0.5% Tween 20, p27, p27/kip1
    MTS
    3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methyoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
    • Received August 27, 1998.
    • Accepted February 12, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 55 (5)
Molecular Pharmacology
Vol. 55, Issue 5
1 May 1999
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology 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.
Growth of Human Tumor Cells in Macroporous Microcarriers Results in p53-Independent, Decreased Cisplatin Sensitivity Relative to Monolayers
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Growth of Human Tumor Cells in Macroporous Microcarriers Results in p53-Independent, Decreased Cisplatin Sensitivity Relative to Monolayers

Barry J. Maurer, Michael A. Ihnat, Cindy Morgan, Janice Pullman, Craig O’Brien, Steven W. Johnson, Janet S. Rasey and Marilyn M. Cornwell
Molecular Pharmacology May 1, 1999, 55 (5) 938-947;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Growth of Human Tumor Cells in Macroporous Microcarriers Results in p53-Independent, Decreased Cisplatin Sensitivity Relative to Monolayers

Barry J. Maurer, Michael A. Ihnat, Cindy Morgan, Janice Pullman, Craig O’Brien, Steven W. Johnson, Janet S. Rasey and Marilyn M. Cornwell
Molecular Pharmacology May 1, 1999, 55 (5) 938-947;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Cysteine151 in Keap1 Drives CDDO-Me Pharmacodynamic Action
  • Allosteric Modulation of Metabotropic Glutamate Receptor 1
  • Mechanism of Selective Action of Paraherquamide A
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics