RNA sequencing of SiHa cells treated with oleic acid and radiation

The impact of obesity on radiation therapy outcome is unclear. Previously, we reported that obese patients with cervical cancer have superior outcomes following chemoradiation. We hypothesized that excess mono- and di- unsaturated fatty acids (uFFAs) enhance response to radiation. Here, using preclinical models, we show that uFFAs radiosensitize cervical cancer through a novel p53-dependent mechanism. UFFAs signaled through PPARgand p53 to promote lipid uptake, storage and metabolism after radiation. Stable isotope labeling confirmed that cervical cancer cells increase both catabolic and anabolic oleate metabolism in response to radiation, with associated increases in dependence on mitochondrial fatty acid oxidation for survival. In vivo, supplementation with exogenous oleate improved tumor growth delay in xenografts after radiation, an effect which could be partially mimicked in tumors from high fat diet induced obese mice. These results suggest that supplementation with uFFAs may improve tumor responses to radiation therapy, particularly in TP53 wild type tumors. Overall design: p53 and PPAR? related gene expression in SiHa Cells SiHa cells 48 hrs after no treatment (Ctrl), 48 hrs after treatment with a single fraction dose of 6 Gy (IR), 48 hrs after treatment with oleic acid (OA) and 48 hrs after treatment oleic acid and radiation (OA + IR)