Ultrasonic cavitation induces necrosis and impairs growth in three-dimensional models of pancreatic ductal adenocarcinoma

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a rapidly increasing cause of mortality whose dismal prognosis is mainly due to overwhelming chemoresistance. New therapeutic approaches include physical agents such as ultrasonic cavitation, but clinical applications require further insights in the mechanisms of cytotoxicity. Three dimensional in vitro culture models such as spheroids exploit realistic spatial, biochemical and cellular heterogeneity that may bridge some of the experimental gap between conventional in vitro and in vivo experiments. Purpose: to assess the feasibility and efficiency of inertial cavitation associated or not with chemotherapy, in a spheroid model of PDAC. Methods: we used DT66066 cells ,derived from a genetically-engineered murine PDAC, isolated from KPC-transgenic mice (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1- Cre). Spheroids were obtained by either a standard centrifugation-based method, or by using a magnetic nano-shuttle method allowi...