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

Biomedicines

卷:10

John M. Baust¹  Robert G. Van Buskirk¹  Kimberly L. Santucci¹  Kristi K. Snyder¹  John G. Baust²  Isaac Raijman³  William E. Fisher⁴ 

[1] CPSI Biotech, Owego, NY 13827, USA;

[2] Center for Translational Stem Cell and Tissue Engineering, Binghamton University, Binghamton, NY 13902, USA;

[3] Department of Medicine-Gastroenterology, Baylor College of Medicine, Houston, TX 77030, USA;

[4] Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA;

关键词: ablation;    cryosurgery;    freeze dose;    pancreatic cancer;    gemcitabine;    oxaliplatin;   

DOI  :  10.3390/biomedicines10020450

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown