Objective: The tumor suppressor gene, p53, plays a pivotal role for cell survival and apoptosis, which could cause different responses to therapeutic agents. Rhenium-188 ((188)Re) decays with the emission of a beta-particle with high energy and is expected to be an important candidate of radiotherapy. We investigated the cellular response of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and the effect of p53 according to beta-irradiation by (188)Re.
Methods: The HCT116 human colon adenocarcinoma cell lines, containing a wild-type p53 (p53(+/+)) and a p53-deleted derivative (p53(-/-)), were gifts from Dr. Bert Vogelstein (Johns Hopkins University, Baltimore, MD). Cells were plated in 24-well plates at 1.0 x 10(5) cells, then (188)Re perrhenate was added and incubated for 24 hours. After irradiation, we performed a cellular uptake assay of (18)F-FDG (370 kBq, 60 minutes). We assayed the hexokinase, cell viability, and cell cycle.
Results: p53-deleted HCT116 cells showed a higher (18)F-FDG uptake and increased hexokinase activity after (188)Re treatment. p53-deleted cells showed a higher G2/M (Gap2/Mitosis) arrest in a relatively low dose of beta-irradiation. However, cell viability was not different, according to the p53 status, after (188)Re treatment.
Conclusions: Therefore, p53 seemed to have a significant role in cellular glucose metabolism and G2/M checkpoint, according to beta-irradiation, and could cause a different therapeutic response of (18)F-FDG uptake in cancer cells.