Due to the advantages of charged particles compared to conventional
radiotherapy, a vast increase is noted in the use of particle
therapy in the clinic. These advantages include an improved dose deposition and increased biological effectiveness.
Metastasis is still an important cause of mortality in
cancer patients and evidence has shown that conventional
radiotherapy can increase the formation of metastasizing cells. An important pathway involved in the process of
metastasis is the Hedgehog (Hh) signaling pathway. Recent studies have demonstrated that activation of the Hh pathway, in response to X-rays, can lead to radioresistance and increased migratory, and invasive capabilities of
cancer cells. Here, we investigated the effect of X-rays,
protons, and
carbon ions on cell survival, migration, and Hh pathway gene expression in
prostate cancer (PC3) and
medulloblastoma (DAOY) cell lines. In addition, the potential modulation of cell survival and migration by the Hh pathway inhibitor
GANT61 was investigated. We found that in both cell lines,
carbon ions were more effective in decreasing cell survival and migration as well as inducing more significant alterations in the Hh pathway genes compared to X-rays or
protons. In addition, we show here for the first time that the Hh inhibitor
GANT61 is able to sensitize DAOY
medulloblastoma cells to particle radiation (
proton and
carbon ion) but not to conventional X-rays. This important finding demonstrates that the results of combination treatment strategies with X-ray
radiotherapy cannot be automatically extrapolated to particle
therapy and should be investigated separately. In conclusion, combining
GANT61 with particle radiation could offer a benefit for specific
cancer types with regard to
cancer cell survival.