A syngeneic orthotopic graft murine model for studying nsPEF effects on peritoneal carcinomatosis tumors

A Taibi , Ml Perrin , J Albouys , C. Yardin , S. Durand-Fontanier (1) , Sylvia M. Bardet (2)

1 CHU Limoges
2 XLIM - XLIM

New immunocompetent cancer models are still needed for the identification and preclinical validation of novel therapeutic targets in colorectal cancer. The aim of this study was to evaluate the implantation rate of CT-26, a type of murine colorectal cancerous cells, on the peritoneum site according to the injection site. The tumor graft efficiency was compared in 4 grafting methods according to the PCI score and using bioluminescence imaging in a syngeneic immunocompetent murine strain. Tumoral growth was then followed by bioluminescence, over 15 days post-grafting and nodules that have been exposed to 10 ns pulses were analyzed by histology. In vitro CT-26 cells were also studied by flow cytometry for their sensitivity to nsPEFs and chemotherapeutic drugs (Mitomycin, Oxyplastin): survival, mitochondrial potential and permeabilization. In parallel, peritoneal tumoral tissue was observed by multiphoton microscopy in order to evaluate the tumor microenvironment. We observed in vitro a strong dose-dependent effect of nsPEF on cell viability, cell death (DAPI, Annexin V), calcium signaling (Fluo-4) and permeabilization (Yo-Pro). In vivo nsPEF exposure of PM nodules shows also dramatic cells death and proliferative inhibition, more efficiently and faster than the ones observed after addition of chemotherapeutic drugs (Mitomycin, Oxyplastin).

Domaines: Sciences du Vivant [q-bio]

A Taibi, Ml Perrin, J Albouys, C. Yardin, S. Durand-Fontanier, et al.. A syngeneic orthotopic graft murine model for studying nsPEF effects on peritoneal carcinomatosis tumors. 3rd World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies, 2019, TOULOUSE, France. ⟨hal-03032390⟩