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
Drug Metabolism & Disposition
  • 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
Drug Metabolism & Disposition

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 dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Expressions of Cytochrome P450, UDP-Glucuronosyltranferase, and Transporter Genes in Monolayer Carcinoma Cells Change in Subcutaneous Tumors Grown As Xenografts in Immunodeficient Nude Mice

Michiko Sugawara, Kiyoshi Okamoto, Tadashi Kadowaki, Kazutomi Kusano, Akiyoshi Fukamizu and Tsutomu Yoshimura
Drug Metabolism and Disposition March 2010, 38 (3) 526-533; DOI: https://doi.org/10.1124/dmd.109.030668
Michiko Sugawara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kiyoshi Okamoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tadashi Kadowaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazutomi Kusano
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akiyoshi Fukamizu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tsutomu Yoshimura
  • 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 + SI
  • PDF
Loading

Abstract

Human tumors grown as xenografts in immunodeficient nude mice are widely used to investigate the pharmacological activities of anticancer drugs. Drug-metabolizing enzymes and transporters are expressed in tumor cell lines and changes in drug metabolism and pharmacokinetics (DMPK)-related gene expression after inoculation of the tumor cell may affect the pharmacological activity of the drug under consideration. The aims of the current study were to characterize DMPK-related gene expression profiles and responses to typical cytochrome P450 inducers in monolayer carcinoma cells grown in tissue culture versus those inoculated into a xenograft model. We used the human hepatocellular carcinoma cell line PLC/PRF/5 for this study and comprehensively assessed changes in DMPK-related gene expression by reverse transcription-polymerase chain reaction quantitation. CYP3A4 and UDP-glucuronosyltransferase 1A protein amounts were also analyzed by immunoprecipitation followed by immunoblotting. We found that the expression of many DMPK-related genes was elevated in the inoculated tumor compared with the monolayer carcinoma cells, indicating changes in their gene regulation pathways, presumably due to modulation of the nuclear receptor family of transcription factors. In addition, monolayer carcinoma versus inoculated tumor cells showed different responses to rifampicin, but similar responses to dexamethasone or 3-methylcholanthrene. These results suggest that inoculation of tumor cells results in the activation of drug metabolism and transport function, leading to changes in the responses to pregnane X receptor ligands and consequent discrepancies in the pharmacological activities between in vitro monolayer carcinoma cells and in vivo xenograft models.

Footnotes

  • This work was supported by Eisai Co., Ltd.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.109.030668.

  • ↵Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • P450
    cytochrome P450
    DMPK
    drug metabolism and pharmacokinetics
    PCR
    polymerase chain reaction
    MC
    3-methylcholanthrene
    Dex
    dexamethasone
    Rif
    rifampicin
    DMSO
    dimethyl sulfoxide
    SLCO
    solute carrier organic anion transporter
    ABC
    ATP-binding cassette
    SLC
    solute carrier
    AhR
    arylhydrocarbon receptor
    ARNT
    AhR nuclear translocator
    HNF
    hepatic nuclear factor
    NR
    nuclear receptor
    PPAR
    peroxisome proliferator-activated receptor
    IPA
    Ingenuity Pathway Analysis
    UGT
    UDP glucuronosyltransferase
    PVDF
    polyvinylidene difluoride
    ALB
    albumin
    AFP
    α-fetoprotein
    FXR
    farnesoid X receptor
    PXR
    pregnane X receptor
    CAR
    constitutive androstane receptor
    LPS
    lipopolysaccharide
    IL
    interleukin
    SN-38
    7-ethyl-10-hydroxycampothecin
    GW4064
    3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid
    Ct
    cycle threshold.

    • Received October 7, 2009.
    • Accepted December 7, 2009.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD 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

Drug Metabolism and Disposition: 38 (3)
Drug Metabolism and Disposition
Vol. 38, Issue 3
1 Mar 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition 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.
Expressions of Cytochrome P450, UDP-Glucuronosyltranferase, and Transporter Genes in Monolayer Carcinoma Cells Change in Subcutaneous Tumors Grown As Xenografts in Immunodeficient Nude Mice
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Expressions of Cytochrome P450, UDP-Glucuronosyltranferase, and Transporter Genes in Monolayer Carcinoma Cells Change in Subcutaneous Tumors Grown As Xenografts in Immunodeficient Nude Mice

Michiko Sugawara, Kiyoshi Okamoto, Tadashi Kadowaki, Kazutomi Kusano, Akiyoshi Fukamizu and Tsutomu Yoshimura
Drug Metabolism and Disposition March 1, 2010, 38 (3) 526-533; DOI: https://doi.org/10.1124/dmd.109.030668

Citation Manager Formats

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

Share
Research ArticleArticle

Expressions of Cytochrome P450, UDP-Glucuronosyltranferase, and Transporter Genes in Monolayer Carcinoma Cells Change in Subcutaneous Tumors Grown As Xenografts in Immunodeficient Nude Mice

Michiko Sugawara, Kiyoshi Okamoto, Tadashi Kadowaki, Kazutomi Kusano, Akiyoshi Fukamizu and Tsutomu Yoshimura
Drug Metabolism and Disposition March 1, 2010, 38 (3) 526-533; DOI: https://doi.org/10.1124/dmd.109.030668
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments.
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CES2-based hydrolysis of molnupiravir
  • Oral PBPK Modeling of Vismodegib
  • Transporter-enzyme interplay in PK of PF-06835919
Show more Articles

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

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics