Adipose-Derived Stem Cells Primed with Paclitaxel Inhibit Ovarian Cancer Spheroid Growth and Overcome Paclitaxel Resistance

Abstract

Adipose-derived stem cells (ADSCs) primed with paclitaxel (PTX) are now hypothesized to represent a potential Trojan horse to vehicle and deliver PTX into tumors. We analyzed the anticancer activity of PTX released by ADSCs primed with PTX (PTX-ADSCs) (~20 ng/mL) in a panel of ovarian cancer (OvCa) cells sensitive or resistant to PTX. We used two (2D) and three dimensional (3D) in vitro models (multicellular tumor spheroids, MCTSs, and heterospheroids) to mimic tumor growth in ascites. The coculture of OvCa cells with PTX-ADSCs inhibited cell viability in 2D models and in 3D heterospheroids (SKOV3-MCTSs plus PTX-ADSCs) and counteracted PTX-resistance in Kuramochi cells. The cytotoxic effects of free PTX and of equivalent amounts of PTX secreted in PTX-ADSC-conditioned medium (CM) were compared. PTX-ADSC-CM decreased OvCa cell proliferation, was more active than free PTX and counteracted PTX-resistance in Kuramochi cells (6.0-fold decrease in the IC50 values). Cells cultivated as 3D aggregated MCTSs were more resistant to PTX than 2D cultivation. PTX-ADSC-CM (equivalent-PTX) was more active than PTX in MCTSs and counteracted PTX-resistance in all cell lines. PTX-ADSC-CM also inhibited OvCa-MCTS dissemination on collagen-coated wells. In conclusion, PTX-ADSCs and PTX-MSCs-CM may represent a new option with which to overcome PTX-resistance in OvCa.

Keywords

• adipose-derived stem cells
• ovarian cancer spheroids
• anticancer chemotherapy
• drug delivery
• paclitaxel resistance