Choline kinase downregulation by siRNA reduces phosphocholine and total choline, and enhances treatment of breast cancer cells with 5-Fluorouracil
Glunde K, Mori N, Takagi T, Venu R, Bhujwalla Z
The Johns Hopkins University School of Medicine
The elevation of phosphocholine (PC) and total choline-containing compounds (tCho) is one of the common features in cancer. Increased choline kinase (ChK) expression and activity may cause this elevation. Here we used small interfering RNA against ChK (siRNA-chk) to knock down ChK expression, and determine its effect on cell viability and proliferation alone and in combination with 5-Fluorouracil (5-FU). Transient siRNA-chk transfection significantly reduced PC and tCho levels detected by 1H NMR spectroscopy in malignant breast cancer cells and significantly decreased cell viability/proliferation to levels comparable with 5-FU alone. Treatment with 5-FU in combination with siRNA-chk transfection enhanced this reduction.