Enhanced Cell Toxicity of Adriamycin by Indomethacin on U251 Glioma Cell

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) can enhance cell toxicity of chemotherapy on tumor cells. In this experiment， indomethacin with non-toxicity dose was screened out. When U251 glioma cells were treated with adriamycin alone or adriamycin combined with low dosage of indomethacin， the cell proliferation and early apoptsis rate were observed by MTT and flow cytometry， respectively. The impacts of indomethacin on ABCG2， MDR1 and MRP1 were detected by RT-PCR and Western blot. The results showed that cell growth was not influenced by 20 μmol/L indomethacin (P>0.05) which was used as a non-toxicity dosage. Compared with control group， proliferation rate was decreased (P<0.05) when exposured to 0.8 mg/L adriamycin or 20 μmol/L indomethacin combined with 0.8 mg/L adriamycin， but proliferation rate was lower in indomethacin combined with adriamycin group than that in adriamycin alone group (P<0.05). The early apoptosis rate was increased in U251 cells treated with 0.8 mg/L adriamycin alone or 20 μmol/L indomethacin combined with 0.8 mg/L adriamycin for 72 h (P<0.01). However， early apoptosis rate was higher in indomethacin combined with adriamycin group than that in adriamycin alone group (P<0.05). The results of RT-PCR and Western blot showed the levels of ABCG2，MDR1 and MRP1 were down-regulated significantly (P<0.05) by indomethacin in a dose-dependent manner. The results suggested that indomethacin enhanced cell toxicity of adriamycin on U251 glioma cells and the mechanisms were involved in down-regulation of drug-resistance genes.

CSTR: 32200.14.cjcb.2013.05.0014