Mathematical description of the effect of HIF inhibition on the radiobiological response of LNCaP cells

The objective of the present study was to evaluate the participation of HIF-1α activation in the radiobiological response of the human prostate adenocarcinoma cell line LNCaP, describing the phenomena with a mathematical model. Four groups were formed under different exposure conditions, including hypoxic cells treated with CoCl2 (300 μM for 22 h) with or without hypoxia-inducible factor inhibitor (150 nM chetomin for 4 h added after an incubation period of 18 h with CoCl2, just before completing the incubation period of 22 h). They were exposed to a source of 60Co in a dose range between 2 and 10 Gy to obtain survival curves that are fitted to a mathematical model. CoCl2 or chetomin treatments do not affect the viability of LNCaP cells that remained unchanged after irradiation. CoCl2 induced hypoxia reduces the survivability of LNCaP, and obstruction of HIF-1α signaling with chetomine produces a slight radioprotective effect. As others report, the genetic reprogramming induced by HIF-1α activation acts as an intrinsic agent that selects cells with more aggressive behavior (Pressley et al., 2017), while chetomin protects cells from death due to its scavenger properties. Interestingly, treatment with chetomin of cells induced to hypoxia (HIF-1 activation with CoCl2) produces a significant reduction in the radioresistance of LNCaP cells, demonstrating that the simultaneous use of chetomin and gamma radiation is an effective option for the treatment of hypoxic prostate cance...
Source: Applied Radiation and Isotopes - Category: Radiology Authors: Source Type: research