Extracellular cGMP Levels Predict the Response of C4-1 Cervical Cancer Cells to Ionizing Radiation

Urine cyclic guanosine monophosphate (cGMP) has been proposed as a prognostic biomarker for therapy response and the risk of relapse of cervical cancer after treatment with radiotherapy (RT). In the present study, an in vitro model with cervical cancer cells (C4-1) was established to determine whether changes in extracellular cGMP levels were predictive for effects of ionization radiation (IR).

During exponential growth, C4-1 cells were exposed to IR with doses between 2 and 12 Gy. The cells were harvested at intervals between one and six days.

The effect of IR on cell growth and extracellular cGMP levels was dose- as well as time-dependent. Three and six days after IR, the cell fractions were reduced with identical sensitivity (ED50 of 1.9 and 1.8 Gy, respectively). The extracellular cGMP levels showed a fall from the first day to sixth day, both in control and after irradiation (2 and 4 Gy), but with somewhat higher levels after IR. However, the extracellular cGMP levels increased after 8 and 12 Gy exposure by 100% and 270%, respectively. When the data were presented as extracellular cGMP levels (% above control), a clear dose- and time-dependency were observed.

From a translational perspective, extracellular cGMP levels may be used to monitor effects and be a potential tool for individualization of radiation therapy (RT).