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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2019

01-09-2019 | Breast Cancer | Preclinical study

Role of docosahexaenoic acid in enhancement of docetaxel action in patient-derived breast cancer xenografts

Authors: Marnie Newell, Susan Goruk, Vera Mazurak, Lynne Postovit, Catherine J. Field

Published in: Breast Cancer Research and Treatment | Issue 2/2019

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Abstract

Purpose

The objective of this study was to investigate if DHA dietary supplementation enhances the anticancer actions of docetaxel (TXT) in two different drug resistant triple negative breast cancer (TNBC) patient-derived xenografts (PDX)s.

Methods

In two experiments, female NSG mice bearing TNBC PDXs were randomized to one of two nutritionally adequate diets (20% w/w): control (0% DHA), or DHA (3.9% w/w of total fat) and injected with 0 or 5 mg/kg TXT, twice weekly for 6 weeks (n = 8 per group). Treatment response was determined by significant differences in tumor weight, and apoptotic, proliferation and cell cycle markers at endpoint.

Results

Mice bearing MAXF574 xenografts fed DHA diet and treated with TXT had a 57% reduction in tumor weight compared to mice fed control diet (P < 0.004), a 64% reduction compared to control + TXT (P < 0.01) and a 34% reduction compared to DHA with no TXT (P < 0.04). DHA + TXT reduced MAXF401 xenografts growth compared to control and control + TXT (by 43% and 34%, respectively, P < 0.05). In both xenografts, DHA + TXT resulted in a higher expression of proapoptotic proteins Ripk1 and Bid, lower expression of proliferation marker Ki67 and anti-apoptotic proteins Bcl-2 and Parp, and a greater increase in cell cycle arrest as measured by decreased Survivin expression when compared to control + TXT mice (P < 0.05).

Conclusions

This work is the first to confirm that DHA supplementation during chemotherapy treatment improves TXT action in two PDX models of TNBC. The results suggest that decreases in tumor size occurred via changes in apoptosis, cell proliferation, and cell cycle pathways.
Appendix
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Metadata
Title
Role of docosahexaenoic acid in enhancement of docetaxel action in patient-derived breast cancer xenografts
Authors
Marnie Newell
Susan Goruk
Vera Mazurak
Lynne Postovit
Catherine J. Field
Publication date
01-09-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05331-8

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