PO-442 Ex vivo prostate cancer culture system recapitulates in vivo response to androgen antagonist

Abstract

IntroductionIn vitro models of prostate cancer (PCa) do not always accurately represent the different stages of PCa nor reliably predict treatment efficacy. Therefore, we have developed an experimental platform in which we cultured tumour slices from patient-derived prostate cancer xenografts (PDX) and tested whether ex vivo PCa culture can recapitulate the in vivo response to the androgen antagonist enzalutamide.Material and methodsIn this ex vivo PDX culture system we used tumours from two PCa models in mice, one androgen receptor (AR) expressing model and one AR-negative model. Tumours were removed from the mice and sliced using a vibratome. We characterised the tumour slices by analysing morphology, cell proliferation, apoptosis, expression levels of AR and excretion of prostate specific antigen (PSA). To test the sensitivity to androgen antagonist, tumour slices from the AD and AI models were treated with enzalutamide.Results and discussionsWe optimised support materials, growth medium and use of a 3D smooth rocking platform to increase oxygen and nutrient exchange. Under optimal condition, the tissue slice cultures maintained morphology, proliferative capacity and viability for at least six days. AR expression was largely maintained and tumour slices continued to secrete PSA in AR expressing tumour slices and responded to enzalutamide with a significant decrease of S-phase cells, increase of apoptotic cells, dramatic reduction of AR expression and inhibition of PSA secretion. As expected, the AR-negative model did not respond to the AR antagonist.ConclusionThis thorough characterisation of PCa PDX tumour slices in an ex vivo culture system showed that the response to enzalutamide recapitulates that observed in vivo. The faithful retention of tissue structure and function in this ex vivo model offers an ideal opportunity for drug screenings, thereby reducing costs and numbers of experimental animals.