Effects of docetaxel on metastatic prostate (DU-145) carcinoma cells cultured as 2D monolayers and 3D multicellular tumor spheroids

Abstract

ABSTRACT Docetaxel (DTX) is one of the chemotherapeutic drugs indicated as a first-line treatment against metastatic prostate cancer (mPCa). This study aimed to compare the impact of DTX on mPCa (DU-145) tumor cells cultured as 2D monolayers and 3D multicellular tumor spheroids (MCTS) in vitro. The cells were treated with DTX (1–96 µM) at 24, 48, or 72 hr in cell viability assays (resazurin, phosphatase acid, and lactate dehydrogenase). Cell death was assessed with fluorescent markers and proliferation by clonogenic assay (2D) and morphology, volume, and integrity assay (3D). The cell invasion was determined using transwell (2D) and extracellular matrix (ECM) (3D). Results showed that DTX decreased cell viability in both culture models. In 2D, the IC50 (72 hr) values were 11.06 μM and 14.23 μM for resazurin and phosphatase assays, respectively. In MCTS, the IC50 values for the same assays were 114.9 μM and 163.7 μM, approximately 10-fold higher than in the 2D model. The % of viable cells decreased, while the apoptotic cell number was elevated compared to the control in 2D. In 3D spheroids, only DTX 24 μM induced apoptosis. DTX (≥24 μM at 216 hr) lowered the volume, and DTX 96 μM completely disintegrated the MCTS. DTX reduced the invasion of mPCa cells to matrigel (2D) and migration from MCTS to the ECM. Data demonstrated significant differences in drug response between 2D and 3D cell culture models using mPCa DU-145 tumor cells. MCTS resembles the early stages of solid tumors in vivo and needs to be considered in conjunction with 2D cultures when searching for new therapeutic targets.