Heterogeneous Responses of Ovarian Cancer Cells to Silver Nanoparticles as a Single Agent and in Combination with Cisplatin

We investigated the effects of silver nanoparticle (AgNP) exposure in three ovarian cancer cell lines (A2780, SKOV3, and OVCAR3). We found that AgNPs were highly cytotoxic toward A2780 and SKOV3 cells but OVCAR3 cells were less sensitive to AgNPs. In agreement with the cytotoxicity data, AgNPs caused DNA damage in A2780 and SKOV3 cells, but not in OVCAR3 cells. A2780 and SKOV3 showed higher levels of basal reactive oxygen species (ROS) relative to OVCAR3 cells. AgNP exposure increased ROS levels in both A2780 and SKOV3 cells, but not in OVCAR3 cells. We found that the heterogeneous cytotoxicity was specific to the uptake of intact particles and was not due to differences in sensitivity to silver ions. Furthermore, the combination of AgNPs and standard-of-care platinum therapy, cisplatin (cis-diamminedichloroplatinum(II), CDDP), was synergistic for treatment of A2780 andOVCAR3 cells and the combination of AgNPs and CDDP showed a favorable dose reduction in all cell lines tested. These results provide insight into potential applications of AgNPs for treatment of ovarian cancer.