Table 2.
Metabolic inhibitors sensitize SKOV3 cultures to cytotoxicity via TRAIL or cisplatin
A | TRAIL | ||||
Untreated | 50 ng/mL | 100 ng/mL | ANOVA | ||
FCCP (μM) | Vehicle | 1.00 ± 0.02a | 0.90 ± 0.06a | 0.93 ± 0.02a | 0.1901 |
1.0 | 0.98 ± 0.04a | 0.85 ± 0.04a* | 0.90 ± 0.02a | 0.0448 | |
2.5 | 0.94 ± 0.03a | 0.75 ± 0.04a** | 0.79 ± 0.01b** | 0.0011 | |
5.0 | 0.91 ± 0.02a | 0.69 ± 0.03b** | 0.72 ± 0.02b** | 7.16E-05 | |
ANOVA | 0.1335 | 0.0143 | 1.28E-06 | ||
B | Cisplatin | ||||
Untreated | 1 μM | 10 μM | ANOVA | ||
FCCP (μM) | Vehicle | 1.00 ± 0.01a | 0.95 ± 0.07a | 1.07 ± 0.04a | 0.2609 |
1.0 | 0.96 ± 0.04a,b | 0.85 ± 0.03a | 0.99 ± 0.04a | 0.1036 | |
2.5 | 0.85 ± 0.00b,c | 0.91 ± 0.05a | 0.95 ± 0.04a | 0.2008 | |
5.0 | 0.80 ± 0.02c | 0.78 ± 0.04a | 0.88 ± 0.02b | 0.1185 | |
ANOVA | 0.0012 | 0.1549 | 0.0384 | ||
C | TRAIL | ||||
Untreated | 50 ng/mL | 100 ng/mL | ANOVA | ||
Oligomycin (μM) | Vehicle | 1.0 ± 0.04a | 0.97 ± 0.04a | 0.95 ± 0.02a | 0.5931 |
1.0 | 0.90 ± 0.01a | 0.85 ± 0.01a | 0.80 ± 0.01b** | 0.006 | |
2.5 | 0.96 ± 0.04a | 0.82 ± 0.05a | 0.81 ± 0.00b | 0.0483 | |
5.0 | 0.86 ± 0.03a | 0.82 ± 0.08a | 0.84 ± 0.04b | 0.9093 | |
ANOVA | 0.0507 | 0.2121 | 0.0062 | ||
Cisplatin | |||||
Untreated | 1 μM | 10 μM | ANOVA | ||
Oligomycin (μM) | Vehicle | 1.00 ± 0.03a | 0.88 ± 0.09a | 0.94 ± 0.02a | 0.3459 |
1.0 | 0.92 ± 0.02a | 0.85 ± 0.01a* | 0.84 ± 0.01b* | 0.0129 | |
2.5 | 0.91 ± 0.02b | 0.84 ± 0.03a | 0.89 ± 0.01a | 0.1578 | |
5.0 | 0.91 ± 0.00b | 0.88 ± 0.03a | 0.84 ± 0.03b | 0.2232 | |
ANOVA | 0.0279 | 0.9114 | 0.0135 |
Resistance of SKOV3 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 indicating significant (* p < 0.05; ** p < 0.01) changes in viability with treatment of cytotoxic agent (A) Pretreatment with FCCP sensitized SKOV3 cultures to TRAIL, (B) but not cisplatin. (C) Culture viability was decreased with oligomycin A treatment prior to TRAIL, (D) as well as cisplatin