05). Highest cytotoxicity
was observed at 72 h and IC50 values of zoledronic acid in OVCAR-3 and MDAH-2774 cells were calculated from cell proliferation plots and were found to be 15.5 and 13 μM, respectively. Figure 2 Effect of zoledronic acid (ZA) on viability of OVCAR-3 and MDAH-2774 cells at 72 h in culture. The data represent the mean of three different experiments (p < 0.05). ATRA and zoledronic acid see more Combination treatment in OVCAR-3 and MDAH-2774 cells To study the possible synergistic/additive effects of ATRA and zoledronic acid combination, OVCAR-3 and MDAH-2774 cells were exposed to different concentrations of each agent alone, and in combination of both for 24, 48 and 72 hours. The synergism or additivity was calculated via CI by using Biosoft Calcusyn Program. Combination of different find more concentrations of ATRA and zoledronic acid were evaluated at different time points (data not shown). Results showed synergistic toxicity in both ovarian cancer cells, OVCAR-3 and MDAH-2774, at 72 h, as compared to any agent alone as shown in table 1. Our
results indicate that 80 nM ATRA and 5 μM zoledronic acid Selleckchem PF 2341066 show 32%- and 18% decrease, respectively, in cell viability of OVCAR-3 cells but the combination of both resulted in 78% decrease in cell viability (figure 3). In MDAH-2774 cells, 40 nM ATRA and 5 μM zoledronic acid show 28%- and 22% decrease, respectively, in cell viability of MDAH-2774 cells but the combination of both resulted in 74% decrease in cell viability (figure 3). Figure 3 Synergistic cytotoxic effects of ATRA and zoledronic acid (ZA) combination on viability of OVCAR-3 and MDAH-2774 cells at 72 h in culture (p < 0.05). Table 1 Combination index values OVCAR-3 Concentration of Drugs CI value Interpretation Zoledronic acid (5 μM) + ATRA (80 nM) 0.688 Synergism Zoledronic acid (10 μM) + ATRA (80
nM) 0.705 Synergism MDAH-2774 Concentration of Drugs CI value Interpretation Zoledronic acid (5 μM) + ATRA (40 nM) 0.010 Synergism Zoledronic acid (5 μM) + ATRA (80 nM) 0.009 Synergism Combination index values of ATRA and zoledronic acid alone and in combination in OVCAR-3 and MDAH-2774 cells. CI values were calculated Resveratrol from the XTT cell viability assays. The data represent the mean of three independent experiments CI a: Combination index ATRA*: All trans retinoic acid The concentrations for each agent found to be synergistic in OVCAR-3 and MDAH-2774 cells are presented in table 1. Effects of the sequential treatment The previous findings demonstrated that tumor cells with ATRA and zoledronic acid resulted in significant synergism at 72 h. Sequential administration of the drugs were carried out to see if either of these drugs enhance the other one’s effect and to understand whether the synergism depended on which agent applied first.