Related Experiment Video

Updated: Jan 15, 2026

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity
07:52

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity

Published on: November 2, 2020

7.0K

NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and

O Dormond1, A Foletti, C Paroz

  • 1Centre Pluridisciplinaire d'Oncologie, University of Lausanne Medical School, Lausanne, Switzerland.

Nature Medicine
|September 5, 2001
PubMed

Insights

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cancer by blocking endothelial-cell cyclooxygenase-2 (COX-2). This suppresses angiogenesis by affecting integrin alpha V beta 3 and small GTPases, hindering tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclooxygenase-2 (COX-2) is overexpressed in many cancers and is a target for nonsteroidal anti-inflammatory drugs (NSAIDs).
  • NSAIDs inhibit cancer development and tumor growth, potentially through anti-angiogenic mechanisms, but the precise pathways are unclear.
  • Integrin alpha V beta 3 is crucial for tumor angiogenesis.

Purpose of the Study:

  • To investigate the mechanism by which NSAIDs suppress tumor angiogenesis.
  • To elucidate the role of endothelial-cell COX-2 in regulating integrin alpha V beta 3 signaling and angiogenesis.

Main Methods:

  • Inhibition of endothelial-cell COX-2 using NSAIDs.
  • Assessment of alpha V beta 3-dependent activation of small GTPases (Cdc42 and Rac).
  • In vitro assays for endothelial-cell spreading and migration.
  • In vivo studies of fibroblast growth factor-2-induced angiogenesis.

Main Results:

  • NSAID-mediated inhibition of endothelial-cell COX-2 suppressed alpha V beta 3-dependent activation of Cdc42 and Rac.
  • Endothelial-cell spreading and migration were inhibited in vitro.
  • Fibroblast growth factor-2-induced angiogenesis was suppressed in vivo.

Conclusions:

  • A novel link exists between COX-2, integrin alpha V beta 3, and Cdc42/Rac-dependent endothelial-cell migration.
  • These findings provide a mechanistic understanding of the anti-angiogenic effects of NSAIDs in cancer therapy.

More Related Videos

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression08:54

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression

Published on: March 29, 2019

7.5K
A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer11:53

A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer

Published on: July 12, 2017

18.9K

Related Concept Videos

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity07:52

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity

Here we describe a rapid and direct in vivo CRISPR/Cas9 screening methodology using ultrasound-guided in utero embryonic lentiviral injections to simultaneously assess functions of several genes in the skin and oral cavity of immunocompetent...
7.0K
In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression08:54

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression

This protocol outlines the steps needed to generate a model system in which the transcription of an endogenous gene of interest can be conditionally controlled in live animals or cells using enhanced lac repressor and/or tet activator...
7.5K
A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer11:53

A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer

This protocol describes the steps for cloning multiple single guide RNAs into one guide RNA concatemer vector, which is of particular use in creating multi-gene knockouts using CRISPR/Cas9 technology. The generation of double knockouts in intestinal organoids is shown as a possible application of this...
18.9K
Generation of Genetically Modified Mice through the Microinjection of Oocytes10:19

Generation of Genetically Modified Mice through the Microinjection of Oocytes

The microinjection of mouse oocytes is commonly used for both classic transgenesis (i.e., the random integration of transgenes) and CRISPR-mediated gene targeting. This protocol reviews the latest developments in microinjection, with a particular emphasis on quality control and genotyping...
21.6K
DNA Vector-based RNA Interference to Study Gene Function in Cancer13:10

DNA Vector-based RNA Interference to Study Gene Function in Cancer

RNA interference (RNAi) possesses many advantages over gene knockout and has been broadly used as a tool in gene functional studies. The invention of DNA vector-based RNAi technology has made long term and inducible gene knockdown possible, and also increased the feasibility of gene silencing in...
21.0K
Quantitative and Automated High-throughput Genome-wide RNAi Screens in C. elegans10:58

Quantitative and Automated High-throughput Genome-wide RNAi Screens in C. elegans

We describe a protocol using C. elegans and RNAi feeding libraries that allows automated measurement of multiple parameters such as fluorescence, size and opacity of individual worms in a population. We give one example of a screen to identify genes involved in anti-fungal innate immunity in C.
18.2K