Table 1.
Metabolic inhibition sensitize KGN cultures to cytotoxicity via TRAIL and cisplatin
A | TRAIL | ||||
Untreated | 50 ng/mL | 100 ng/mL | ANOVA | ||
FCCP (μM) | Vehicle | 1.00 ± 0.01a | 0.83 ± 0.06a* | 0.97 ± 0.04a | 0.0206 |
1.0 | 0.94 ± 0.02a | 0.84 ± 0.06a,b | 0.85 ± 0.04a,b | 0.1921 | |
2.5 | 0.74 ± 0.05b | 0.74 ± 0.04b | 0.74 ± 0.04b | 0.9967 | |
5.0 | 0.68 ± 0.05b | 0.44 ± 0.02c | 0.49 ± 0.06c* | 0.0327 | |
ANOVA | 2.30E-06 | 2.82E-06 | 7.48E-08 | ||
B | Cisplatin | ||||
Untreated | 1 μM | 10 μM | ANOVA | ||
FCCP (μM) | Vehicle | 1.00 ± 0.10a | 1.21 ± 0.16a | 0.98 ± 0.06a | 0.3321 |
1.0 | 0.93 ± 0.07a | 1.03 ± 0.12a | 0.81 ± 0.03b | 0.1766 | |
2.5 | 0.91 ± 0.03a | 0.97 ± 0.16a | 0.79 ± 0.01b | 0.4927 | |
5.0 | 0.79 ± 0.03a | 0.89 ± 0.08a | 0.59 ± 0.03c* | 0.0155 | |
ANOVA | 0.1798 | 0.427 | 0.0005 | ||
C | TRAIL | ||||
Untreated | 50 ng/mL | 100 ng/mL | ANOVA | ||
Oligomycin (μM) | Vehicle | 1.00 ± 0.05a | 1.15 ± 0.08a | 0.96 ± 0.02a | 0.1381 |
1.0 | 0.99 ± 0.08a | 1.01 ± 0.03a | 0.81 ± 0.01b | 0.0511 | |
2.5 | 1.00 ± 0.07a | 0.97 ± 0.01a | 0.82 ± 0.02b* | 0.0368 | |
5.0 | 1.06 ± 0.02a | 0.97 ± 0.03a | 0.83 ± 0.02b* | 0.0013 | |
ANOVA | 0.8191 | 0.0827 | 0.0013 | ||
D | Cisplatin | ||||
Untreated | 1 μM | 10 μM | ANOVA | ||
Oligomycin (μM) | Vehicle | 1.00 ± 0.05a | 0.85 ± 0.04a | 0.65 ± 0.07a | 0.0144 |
1.0 | 1.08 ± 0.06a | 1.03 ± 0.08a | 0.84 ± 0.02b | 0.0548 | |
2.5 | 1.03 ± 0.03a | 1.05 ± 0.07a | 0.83 ± 0.02b* | 0.0293 | |
5.0 | 0.98 ± 0.02a | 0.94 ± 0.03a | 0.77 ± 0.06b* | 0.0206 | |
ANOVA | 0.4821 | 0.161 | 0.0802 |
Resistance of KGN cultures to cell death inducing agents TRAIL or cisplatin was analyzed through inhibition of OXPHOS using oligomycin A and a mitochondrial membrane potential uncoupler, FCCP, using MTS viability assays. Results are presented as fold change to vehicle treated control cultures with differing letters indicating significant (p < 0.05) changes in viability with treatment of inhibitor, and asterisks (* p < 0.05) indicating significant changes in viability with treatment of cytotoxic agent. (A) Sequential treatment with FCCP and TRAIL resulted in decreases in culture viability over control samples. (B) Culture viability also decreased with FCCP treatment prior to addition of cisplatin. (C) Oligomycin A pretreatment sensitized KGN cells to both TRAIL and (D) cisplatin