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Intraductal Injection for Localized Drug Delivery to the Mouse Mammary Gland
Published on: October 4, 2013
Therapeutic treatment of DMBA-induced mammary tumors with PPAR ligands
G M Pighetti1, W Novosad, C Nicholson
1Department of Dairy and Animal Science, University of Tennessee, 114B McCord, 2640 Morgan Circle Drive, Knoxville, TN 37996, USA. gpighetti@utk.edu
Abstract:
The objective of this study was to evaluate the ability of troglitazone (a thiazolidinedione) and Wy-14,643 (a clofibrate) to inhibit progression of non-detectable and detectable mammary tumors in rats induced by 7,12 dimethylbenz(a)anthracene (DMBA) when compared to those receiving no treatment or tamoxifen. Although not as effective as tamoxifen in decreasing overall tumor incidence, Wy-14,643 reduced the percentage and number of malignant tumors that developed when compared to both troglitazone and control. Treatment of detectable tumors with either Wy-14,643 or troglitazone induced regression or stasis of total tumor volume in 40-50% of the animals, compared to only 10% in control and 65% in tamoxifen treated animals. Moreover, each PPAR ligand was as effective as tamoxifen in preventing additional tumor development. In summary, both PPAR ligands were more effective than no treatment in preventing tumor progression once detected. However, only the PPAR-alpha activator, Wy-14,643 was able to reduce the development of malignant tumors when administered prior to detection.
Insights
Wy-14,643 and troglitazone, PPAR ligands, slowed mammary tumor growth in rats. Wy-14,643 also reduced malignant tumor development, showing promise in cancer research.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Mammary tumors are a significant health concern.
- 7,12-dimethylbenz(a)anthracene (DMBA) is a known carcinogen used to induce mammary tumors in research models.
- Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in various metabolic processes and have been implicated in cancer development.
Purpose of the Study:
- To evaluate the efficacy of troglitazone (a thiazolidinedione) and Wy-14,643 (a clofibrate), both PPAR ligands, in inhibiting the progression of DMBA-induced mammary tumors in rats.
- To compare the effects of these PPAR ligands with no treatment and tamoxifen, a standard breast cancer treatment.
Main Methods:
- Rats were induced with DMBA to develop mammary tumors.
- Tumor progression was monitored in groups treated with troglitazone, Wy-14,643, tamoxifen, or no treatment.
- Tumor incidence, malignancy, regression, stasis, and additional tumor development were assessed.
Main Results:
- Wy-14,643 reduced the incidence of malignant tumors compared to troglitazone and controls.
- Both Wy-14,643 and troglitazone induced regression or stasis of tumor volume in 40-50% of animals with detectable tumors, outperforming controls (10%) but less than tamoxifen (65%).
- Both PPAR ligands were effective in preventing additional tumor development, similar to tamoxifen.
Conclusions:
- PPAR ligands, particularly Wy-14,643, show potential in managing mammary tumor progression.
- Wy-14,643, a PPAR-alpha activator, demonstrated a unique ability to reduce malignant tumor development when administered early.
- These findings suggest PPAR ligands could be a valuable therapeutic strategy in oncology, warranting further investigation.

