Post-treatment recovery of docetaxel-treated prostate cancer monolayer and spheroid culture

Abstract

In the last half-century, it has become widely recognized that small 3D aggregates of cancer cells called tumor spheroids mimic some aspects of tumor behavior. Cell culture geometry has been shown to influence drug pharmacokinetics, delivery, and resistance. Despite the improved physiological relevance, the laborious nature of spheroids has limited clonogenic measurement and longitudinal observation of post-treatment recovery in docetaxel-treated prostate tumor spheroids. Agent-based modeling can complement spheroid experiments by probing questions of interest that are experimentally inaccessible. Here, we performed proliferation and clonogenic assays in docetaxel-treated PC3 cells cultured in monolayers and spheroids to assess and compare end-of-treatment survival and post-treatment recovery. We observed growth stimulation with no survival benefit in low dose docetaxel-treated monolayer and spheroid culture. However, agent-based modeling suggested that this hormetic effect may have been influenced by the active process of apoptosis. To the best of our knowledge, this is the first clonogenic measurement of docetaxel-treated spheroid culture and longitudinal observation of post-treatment docetaxel-dose dependent effects in prostate cancer cell culture.