Related Experiment Video
Updated: Aug 2, 2026
High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
Strategy for developing transgenic assays for screening antineoplastic drugs that affect tubulin polymerization
G M Porter1, L Armstrong, L L Nielsen
1Department of Laboratory Animal Medicine & Surgery, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Abstract:
In this study we evaluated the antitumor efficacy of taxol in four solid tumor models derived from wap-ras line 69 transgenic mice. Taxol inhibited the growth of spontaneous salivary and mammary gland adenocarcinomas in wap-ras mice. In nude mice it was also effective against solid tumors caused by WR21 cells derived from a wap-ras salivary gland tumor. Taxol was not able to prevent tumor emergence in wap-ras/F mice, a subline of the wap-ras strain in which all males develop palpable mammary gland tumors between 1.5 and 3.0 months of age. Our data indicate the range of results that can be expected when this panel of related transgenic tumor models is used to study the antitumor effects of taxol and other therapeutic drugs that act by affecting tubulin polymerization. These models of ras-mediated neoplasia should prove useful for testing anticancer compounds with taxol-like mechanisms of action.
Insights
This study shows Taxol effectively inhibits tumor growth in several mouse models. However, it did not prevent tumor emergence in a specific rapidly developing mammary tumor model.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Transgenic mouse models are crucial for evaluating anticancer drug efficacy.
- Ras-mediated neoplasia provides a platform for studying tumor development and therapeutic interventions.
- Taxol (paclitaxel) is a well-established chemotherapy agent targeting tubulin polymerization.
Purpose of the Study:
- To assess the antitumor efficacy of Taxol in diverse solid tumor models derived from wap-ras transgenic mice.
- To determine the effectiveness of Taxol against spontaneous and induced tumors in these models.
- To evaluate the utility of these specific transgenic tumor models for preclinical drug testing.
Main Methods:
- Utilized four solid tumor models from wap-ras line 69 transgenic mice.
- Administered Taxol to evaluate its impact on tumor growth and emergence.
- Tested Taxol efficacy in both syngeneic wap-ras mice and in nude mice xenografted with tumor cells.
Main Results:
- Taxol demonstrated significant inhibition of spontaneous salivary and mammary gland adenocarcinomas in wap-ras mice.
- Taxol was effective against solid tumors induced by WR21 cells in nude mice.
- Taxol failed to prevent tumor emergence in the wap-ras/F subline, characterized by rapid mammary tumor development.
Conclusions:
- The evaluated transgenic tumor models exhibit variable responses to Taxol, highlighting the importance of model selection for drug efficacy studies.
- These ras-mediated neoplasia models are valuable for preclinical assessment of anticancer drugs targeting tubulin polymerization.
- The findings provide insights into the spectrum of Taxol's activity and the utility of these models for future cancer drug discovery.
