Chemo-sensitivity of Two-dimensional Monolayer and Three-dimensional Spheroid of Breast Cancer MCF-7 Cells to Daunorubicin, Docetaxel, and Arsenic Disulfide

Chemo-sensitivity of two-dimensional (2D) monolayers and three-dimensional (3D) spheroids of human breast cancer MCF-7 cells were investigated.MCF-7 cells were cultured in monolayers or spheroids established using a thermo-reversible gelatin polymer, in the presence of daunorubicin, docetaxel, or As2S2 Cell proliferation was examined by a Cell Counting Kit-8 assay.Daunorubicin, docetaxel, and As2S2 dose-dependently decreased the MCF-7 cell proliferation in both 2D- and 3D-culture systems. The 3D spheroids were less sensitive to these agents than the 2D cultured cells. Verapamil, an inhibitor of P-glycoprotein, partially enhanced the antiproliferative effects of the agents. DL-buthionine-(S, R)-sulfoximine significantly increased (p<0.05), while N-acetyl-L-cysteine significantly inhibited the antiproliferative effects of As2S2 (p<0.003).The 3D spheroids showed less sensitivity to the antiprolliferative efficacies of anticancer agents than the 2D cultured cells. P-Glycoprotein is suggested to be partially implicated in drug resistance. Reduction of cellular glutathione level enhanced the As2S2 cytotoxicity.