Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice

Breast cancer cells modulate lipid and fatty acid metabolism to sustain proliferation. The role of adipocytes in cancer treatment efficacy remains, however, to be fully elucidated. We investigated whether diet-induced obesity (DIO) affects the efficacy of doxorubicin treatment in a breast tumor-bear...

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Published inFrontiers in oncology Vol. 10; p. 306
Main Authors Mentoor, Ilze, Nell, Theo, Emjedi, Zaakiyah, van Jaarsveld, Paul J, de Jager, Louis, Engelbrecht, Anna-Mart
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 17.03.2020
Subjects
adipose tissue
breast cancer
fatty acids
obesity
Oncology
treatment efficacy
adipose tissue
breast cancer
fatty acids
obesity
treatment efficacy
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Summary:Breast cancer cells modulate lipid and fatty acid metabolism to sustain proliferation. The role of adipocytes in cancer treatment efficacy remains, however, to be fully elucidated. We investigated whether diet-induced obesity (DIO) affects the efficacy of doxorubicin treatment in a breast tumor-bearing mouse model. Female C57BL6 mice were fed a high fat or low fat diet for the full duration of the study (12 weeks). After 8 weeks, mice were inoculated with E0771 triple-negative breast cancer cells in the fourth mammary gland to develop breast tumor allographs. Tumor-bearing mice received either vehicle (Hank's balanced salt solution) or doxorubicin (chemotherapy). Plasma inflammatory markers, tumor, and mammary adipose tissue fatty acid composition, as well as protein expression of lipid metabolism markers were determined. The high fat diet (HFD) attenuated the treatment efficacy of doxorubicin. Both leptin and resistin concentrations were significantly increased in the HFD group treated with doxorubicin. Suppressed lipogenesis (decreased stearoyl CoA-desaturase-1) and lipolysis (decreased hormone-sensitive lipase) were observed in mammary adipose tissue of the DIO animals, whereas increased expression was observed in the tumor tissue of doxorubicin treated HFD mice. Obesogenic conditions induced altered tissue fatty acid (FA) compositions, which reduced doxorubicin's treatment efficacy. In mammary adipose tissue breast cancer cells suppressed the storage of FAs, thereby increasing the availability of free FAs and favored inflammation under obesogenic conditions.
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Edited by: Federica Sotgia, University of Salford, United Kingdom
This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology
Reviewed by: Cesare Indiveri, University of Calabria, Italy; Olivier Peulen, University of Liège, Belgium
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2020.00306