Enhancing prostate cancer cryotherapy using tumour necrosis factor related apoptosis-inducing ligand (TRAIL) sensitisation in an in vitro cryotherapy model

Cryotherapy is a minimally invasive treatment for prostate cancer. Complete ablation of cancer tissue some times fails and results in disease recurrence. In this study we investigate the effect of TRAIL as a sensitising agent to enhance the effects of cryotherapy on prostate cancer cells. Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. The effects of TRAIL, cryotherapy or combination of both treatment on DU-145 and PC-3 were evaluated. Viability and mode of cell death was assessed following treatment. Cryotherapy did not result in complete cell death at temperature −40 °C. Cells died by both necrosis and apoptosis. Cells which survived freeze–thaw cycle became more sensitive to a second freezing injury. TRAIL resulted in minimal cell death. Concomitant treatment of the tumour cells with TRAIL and cryotherapy resulted in complete loss of viability at −10 and −20 °C. Cell death was mainly due to marked increase in necrosis.Our finding demonstrates that combined treatment of TRAIL and cryotherapy represent a novel approach to increase the sensitivity to cryotherapy. This combined approach may be feasible for locally advanced prostate cancer.