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Abstract #0843

Molecular Effects of the Chemotherapeutic Drug Doxorubicin on Choline Phospholipid Metabolism of Breast Cancer Cells

Menglin Cheng1, Asif Rizwan1, Zaver M. Bhujwalla1,2, Lu Jiang1, and Kristine Glunde1,2

1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

This study shows that the widely used chemotherapeutic drug doxorubicin increases the 1H or 31P MRS detectable glycerophosphocholine (GPC) concentration, while decreasing the phosphocholine (PC) concentration in human MCF-7 and MDA-MB-231 breast cancer cell lines. This GPC increase and PC decrease was caused by doxorubicin-induced decreases in the expression of the GPC-phosphodiesterase GDPD6, choline kinase α, and phospholipase D1. GDPD6 silencing was able to counteract the doxorubicin-induced promotion of breast cancer cell migration, which can occur at low doxorubicin concentrations. GPC, PC, and PC/GPC may serve as non-invasive surrogate makers of therapeutic response in breast cancer patients undergoing doxorubicin chemotherapy.

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