DNA damage-induced DR5 up-regulation and synergistic cytotoxicity by combination treatment with TRAIL and genotoxic agents in human glioma cell lines
Cells were treated with drugs for 16 h for RNA preparation and 24 h for cytotoxicity assays.
| Cell line . | DR5 up-regulation . | . | . | Synergistic cytotoxicitya . | . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| . | CDDP (μg/ml) . | VP16 (μg/ml) . | BCNU (μM) . | CDDPb + TRAILc . | VP16b + TRAILc . | BCNUb + TRAILc . | ||||
| Responders | ||||||||||
| U87MG | + (4) | + (16) | ± (100) | + | + | − | ||||
| A1207 | + (10) | + (16) | + (200) | + | + | + | ||||
| U178MG | + (4) | + (16) | + (100) | + | + | − | ||||
| LN229 | + (10) | + (16) | − (100) | + | + | − | ||||
| U251MG | + (4) | + (8) | + (200) | + | + | + | ||||
| LN428 | + (10) | + (64) | − (300) | + | + | ± | ||||
| Intermediate-responder | ||||||||||
| T98G | ± (10) | − (128) | − (200) | ± | − | − | ||||
| Nonresponders | ||||||||||
| U373MG | − (40) | − (128) | ± (100) | − | − | − | ||||
| LNZ308 | − (40) | − (128) | − (100) | − | − | − | ||||
| Cell line . | DR5 up-regulation . | . | . | Synergistic cytotoxicitya . | . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| . | CDDP (μg/ml) . | VP16 (μg/ml) . | BCNU (μM) . | CDDPb + TRAILc . | VP16b + TRAILc . | BCNUb + TRAILc . | ||||
| Responders | ||||||||||
| U87MG | + (4) | + (16) | ± (100) | + | + | − | ||||
| A1207 | + (10) | + (16) | + (200) | + | + | + | ||||
| U178MG | + (4) | + (16) | + (100) | + | + | − | ||||
| LN229 | + (10) | + (16) | − (100) | + | + | − | ||||
| U251MG | + (4) | + (8) | + (200) | + | + | + | ||||
| LN428 | + (10) | + (64) | − (300) | + | + | ± | ||||
| Intermediate-responder | ||||||||||
| T98G | ± (10) | − (128) | − (200) | ± | − | − | ||||
| Nonresponders | ||||||||||
| U373MG | − (40) | − (128) | ± (100) | − | − | − | ||||
| LNZ308 | − (40) | − (128) | − (100) | − | − | − | ||||
More than 20% increase in the percentage of growth inhibition than simple addition of the percentage of growth inhibition of the two drugs was evaluated as +, more than 10% increase as ±.
At the same concentrations used in the treatment for DR5 up-regulation. Single treatment with each of these drugs at the same concentrations was ineffective in all cell lines.
TRAIL (0.1 μg/ml) was used for all combination treatments. Single treatment with 10 μg/ml TRAIL was ineffective in all cell lines.