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Inhibitory effects of paclitaxel combined with TRAIL on human glioma U87 cells and the possible mechanism
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Abstract:
Objective:To investigate the inhibitory effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combined with paclitaxel treatment on human glioma U87 cells and the possible mechanism. Methods: MTT assay was used to detect the proliferation inhibitory rates of U87 cells in the paclitaxel group, TRAIL group, and TRAIL/paclitaxel combination group, and flow cytometry was used to detect the effects of different treatments on apoptosis of U87 cells. The expression levels of TRAIL death receptor (DR) 4, DR5, caspase-8 and caspase-3 in U87 cells after different treatments were measured by Western blotting. Results: MTT results showed the TRAIL or paclitaxel used alone demonstrated a favorable inhibitory effect on proliferation of U87 cells in a concentration-dependent manner. Combined application of TRAIL (500 ng/ml) and paclitaxel (0.5 μmol/L) showed a synergistic inhibitory effect on the proliferation of U87 cells with the coefficient of drug interaction (CDI) being 0.59. The proliferation inhibitory rate of U87 cells in the combination group was significantly higher than that in the TRAIL or paclitaxel used alone groups (\[70.24±368\] % vs \[2701±2.36\] %, \[21.31±4.85\] %, P<0.01). The apoptotic rate of U87 cells in the TRAIL/paclitaxel combination group was significantly higher than that in the control group, TRAIL group, or paclitaxel group (\[67.67±2.46\] % vs \[1.80±1.13\] %, \[22.13±2.18\] %, \[35.90±2.53\]%, P<0.01). The up-regulation expressions DR4, caspase-8 and caspase-3 in U87 cells was more obvious in TRAIL/paclitaxel combination treatment group than that in the TRAIL or paclitaxel groups (P<0.05). However, no obvious change in DR5 xpression was observed (P>0.05). Conclusion: TRAIL combined with paclitaxel treatment can up-regulate DR4, caspase-8 and caspase-3 expressions, thereby inhibiting the proliferation and inducing the apoptosis of U87 cells.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81000565)
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