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Novel Adjuvants Of Cryotherapy To Enhance Direct and Bystander Killing Of Human Prostate Cancer Cells (PC3)
Mary Ann K Kenneson, Daniel B Rukstalis, Mansoor Ahmed*, Sara Boyer*
Geisinger Medical Center, Danville, PA
Introduction: Cryoablation of the prostate is a promising minimally invasive approach to cancer therapy. However, there is a 7% - 25% positive re-biopsy rate after cryotherapy. To decrease local recurrence, novel adjuvants for cryoablation are proposed. We hypothesize that the combined effects of single dose radiation or curcumin will synergize the effects of cryoablation induced clonogenic inhibition in a human prostate cancer cell line (PC3).
Method: A Confluent culture of PC3 cells were exposed to -5°C, -10°C, and -20°C for 30 minutes and thawed at 37°C. A single cell suspension from these flasks was prepared for clonogenic assay. In combination experiments curcumin (IC50) or single dose radiation (5 Gy) was given 24 hours pre or post cryotherapy. To assess the bystander effects of cryoablation, cryoablation conditioned media (CCM) was obtained 24 hours post cryoablation. CCM was exposed to single cell PC3 cultures for colony forming assay.
Results: PC3 cells showed a dose dependent decrease in surviving fractions (SF) 82%, 44% and 1% in response to -5°C, -10°C, and -20°C respectively. Pre treatment with the curcumin in the cur/-10°C combination group showed a significant decrease in SF compared to curcumin alone, 40% vs 75%. CCM also caused enhanced clonogenic inhibition. The SF were 38%, 25% and 17% respectively in -10°C, 5 Gy and -10°C/Radiation combination treatment groups.
Conclusions: This study demonstrated that adjuvant radiation and curcumin have a synergistic effect with cryoablation. Current studies are underway to assess cell death and understand the molecular mechanism of this synergistic effect.
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