107 - Ascorbate Decreases Circulating Tumor Cells (CTCs) in Mice with Pancreatic Adenocarcinoma (PDAC)

Abstract

Circulating tumor cells (CTCs) are intact cells, the closest representation of human tissue compatible with immunohistochemistry and traditional pathology protocols. Importantly, CTCs are thought to play a central role in metastatic disease spread by detaching from primary disease sites, entering circulation, and seeding distant tissues. Pharmacological ascorbate has shown promise as a potential adjuvant for advanced pancreatic cancer (PDAC) treatment through its ability to generate H2O2 leading to selective cancer cytotoxicity. The study presented here utilizes an animal model and newly developed PDAC CTC assay to reliably determine the effect of ascorbate treatment on the concentration of CTCs. MIA PaCA-2 human PDAC cells were transfected with pQClucIN and pMSCV-IRES-GFP plasmids to express luciferase and green fluorescent protein (GFP) and facilitate in vivo bioluminescent imaging. A 20 µL matrigel slurry was prepared to suspend 4 x 105 cells for orthotopic intrapancreatic injection into 16 nude mice under ultrasound guidance. On day 35, 10 control mice began twice daily saline injections (4 g/kg) and 6 treatment mice began BID ascorbate injections (4 g/kg). On day 50, CTCs were analyzed by flow cytometry to detect circulating GFP-expressing cancer cells. Tumor growth over time, as measured by bioluminescent imaging signal strength, increased equally between groups prior to treatment but slowed significantly in mice treated with pharmacological ascorbate compared to control (p