One of the most lethal carcinomas is pancreatic cancer. As standard treatment using chemotherapy and radiation has shown limited success, thermal regimens (cryotherapy or heat ablation) are emerging as viable alternatives. Although promising, our understanding of pancreatic cancer response to thermal ablation remains limited. In this study, we investigated the thermal responses of 2 pancreatic cancer cell lines in an effort to identify the minimum lethal temperature needed for complete cell death to provide guidance for in vivo applications. PANC-1 and BxPC-3 were frozen (À10 C to À25 C) or heated (45 C-50 C) in single and repeated exposure regimes. Posttreatment survival and recovery were analyzed using alamarBlue assay over a 7-day interval. Modes of cell death were assessed using fluorescence microscopy (calcein acetoxymethyl ester/propidium iodide) and flow cytometry (YO-PRO-1/propidium iodide). Freezing to À10C resulted in minimal cell death. Exposure to À15 C had a mild impact on PANC-1 survival (93%), whereas BxPC-3 was more severely damaged (33%). Exposure to À20 C caused a significant reduction in viability (PANC-1 ¼ 23%; BxPC-3 ¼ 2%) whereas À25 C yielded complete death. Double freezing exposure was more effective than single exposure. Repeat exposure to À15 C resulted in complete death of BxPC-3, whereas À20 C severely impacted PANC-1 (7%). Heating to 45 C resulted in minimum cell death. Exposure to 48 C yielded a slight increase in cell loss (PANC-1 ¼ 85%; BxPC-3 ¼ 98%). Exposure to 50 C caused a significant decline (PANC-1 ¼ 70%; BxPC-3 ¼ 9%) with continued deterioration to 0%. Double heating to 45 C resulted in similar effects observed in single exposures, whereas repeated 48 C resulted in significant increases in cell death (PANC-1 ¼ 68%; BxPC-3 ¼ 29%). In conclusion, we observed that pancreatic cancer cells were completely destroyed at temperatures <À25 C or >50 C using single thermal exposures. Repeated exposures resulted in increased cell death at less extreme temperatures. Our data suggest that thermal ablation strategies (heat or cryoablation) may represent a viable technique for the treatment of pancreatic cancer.
Pancreatic cancer (PaCa) is one of the leading causes of cancer related deaths in the world today. It is estimated that 95% of patients diagnosed with PaCa will die because of limited treatment options. As standard treatments have not yielded an improvement in patient outcome, alternative approaches, such as thermal ablation, may offer a new treatment path. We previously reported the lethal temperatures necessary for PaCa ablation for both freeze and heat based treatments. In this study, we investigated the response of PaCa cells in vitro to a combination treatment of heating and freezing, dual thermal ablation (DTA), in an effort to further improve ablation efficacy.PaCa cell lines, PANC-1 and BxPC-3, were subjected to heating (45 to 50°C), freezing (-10 to -20°C), or DTA exposure. Post-exposure viability was assessed over a 7-day recovery interval. Modes of cell death were analyzed using fluorescence microscopy and flow cytometry.Our results indicated that in comparison to single thermal modalities, DTA resulted in greater cell destruction at a more rapid rate. Specifically, -15°C had a moderate impact on day one cell viability (PANC-1=80%; BxPC-3=21%) and 50°C (PANC-1=74%; BxPC-3=18%) caused a slow decline in cell number post-treatment. The combination of these treatments resulted in an increased cell death one-day post-treatment (PANC-1=28%; BxPC-3=5%) and achieved complete cell destruction within three days. Overall, these data suggest that a combination of heat and freeze ablation, DTA, may provide for an improved treatment strategy for PaCa.
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