[Assay system for tumor control effect using encapsulated multicellular spheroid models]

Most advanced head and neck cancers are inoperable, hence they are treated by either radiotherapy or combined chemoradiotherapy. More effective methods of combined chemoradiotherapy are certainly required for improving the curability of these cancers. Numerous factors involved in modifying the effectiveness have to be quantitatively analyzed for improvement; this has been a limiting factor preventing therapeutic progress. The purpose of the present study was to establish an experimental technique for assessing the in vivo effect of radiotherapy or chemoradiotherapy on multicellular tumor spheroids encapsulated in a semitransparent microcapsule. Mouse squamous carcinoma cells suspended in sodium alginate solution were transferred to a syringe connected to an air jet apparatus. Droplets containing cells were dropped into a calcium chloride solution, which caused them to gel, and then treated with poly L-lysine solution. The encapsulated cells were cultured in vitro for three weeks to form multicellular spheroids with central necrosis. The spheroids were either X-irradiated in vitro or in vivo by grafting in a nude mouse. The dose-cell survival curve in vivo was biphasic with a radioresistant component which was not observed in vitro. This method was considered to be applicable to human tumor cells and useful for determining the effectiveness of therapeutic agent as human solid tumor models in vivo.