An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

Abstract

As the incidence of pancreatic ductal adenocarcinoma (PDAC) continues to grow, so does the need for new strategies for treatment. One such area being evaluated is cryoablation. While promising, studies remain limited and questions surrounding basic dosing (minimal lethal temperature) coupled with technological issues associated with accessing PDAC tumors and tumor proximity to vasculature and bile ducts, among others, have limited the use of cryoablation. Additionally, as chemotherapy remains the first-line of attack for PDAC, there is limited information on the impact of combining freezing with chemotherapy. As such, this study investigated the in vitro response of a PDAC cell line to freezing, chemotherapy, and the combination of chemotherapy pre-treatment and freezing. PANC-1 cells and PANC-1 tumor models were exposed to cryoablation (freezing insult) and compared to non-frozen controls. Additionally, PANC-1 cells were exposed to varying sub-clinical doses of gemcitabine or oxaliplatin alone and in combination with freezing. The results show that freezing to −10 °C did not affect viability, whereas −15 °C and −20 °C resulted in a reduction in 1 day post-freeze viability to 85% and 20%, respectively, though both recovered to controls by day 7. A complete cell loss was found following a single freeze below −25 °C. The combination of 100 nM gemcitabine (1.1 mg/m2) pre-treatment and a single freeze at −15 °C resulted in near-complete cell death (<5% survival) over the 7-day assessment interval. The combination of 8.8 µM oxaliplatin (130 mg/m2) pre-treatment and a single −15 °C freeze resulted in a similar trend of increased PANC-1 cell death. In summary, these in vitro results suggest that freezing alone to temperatures in the range of −25 °C results in a high degree of PDAC destruction. Further, the data support a potential combinatorial chemo/cryo-therapeutic strategy for the treatment of PDAC. These results suggest that a reduction in chemotherapeutic dose may be possible when offered in combination with freezing for the treatment of PDAC.

Caffeic acid, a dietary polyphenol pre-sensitizes PDAC to chemotherapeutic drug

“…Moreover, CFA is more affective on Mia-PaCa-2 as compared to Panc-1 indicating more resistance in Panc-1 than Mia-PaCa-2. Higher resistance of Panc-1 cell lines to discrete therapeutics is also reported in earlier reports [45,46]. After obtaining the IC 50 concentrations on both cell lines, effect of CFA on migration properties was checked.…”

Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies

“…The in vitro effect of cryoablation has been studied in multiple articles. For example, Baust et al subjected PDAC-1 cell lines to cryoablation, chemotherapy of GEM/or oxaliplatin, and a combination of these two modalities [ 177 ]. The findings from this study suggested that a temperature of −15 °C showed partial cell death, while complete cell death could be achieved at −25 °C only.…”

Complications Risk Assessment and Imaging Findings of Thermal Ablation Treatment in Liver Cancers: What the Radiologist Should Expect

“…Different diagnostic tools may be employed, alone or in association [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Computed tomography (CT) and magnetic resonance imaging (MRI) represent the traditional imaging tools employed during the pre-treatment phase in order to identify and assess the target area [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ], and in surveillance of the patient to evaluate treatment efficacy and post-procedural complications [ 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. Ultrasound examination (US), without or with contrast medium (CEUS), is an innovative tool, utilized for problem solving during pre- and post-treatment phases [ 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ], although the main use of interest is the possibility of assessing immediate effects during the procedure [ 60 , 61 ].…”