Abstract #0843

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

Menglin Cheng¹, Asif Rizwan¹, Zaver M. Bhujwalla^1,2, Lu Jiang¹, and Kristine Glunde^1,2

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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