摘要
非甾体类抗炎药物(nonsteroidal anti-inflammatory drugs,NSAIDs)能增强化疗药物对肿瘤细胞的细胞毒性作用。该研究首先筛选出无细胞毒性剂量的吲哚美辛,采用MTT法和流式细胞仪分别检测阿霉素或阿霉素联合低剂量吲哚美辛对U251细胞增殖和早期凋亡的影响;并应用RT-PCR和Western blot检测吲哚美辛对ABCG2、MDR1和MRP1的影响。结果显示,20μmol/L吲哚美辛对胶质瘤U251细胞无显著生长抑制(P>0.05),可作为无细胞毒性剂量使用;0.8 mg/L阿霉素组和20μmol/L吲哚美辛联合0.8 mg/L阿霉素组与对照组相比细胞增殖显著下降(P<0.05),且吲哚美辛联合阿霉素组较单独使用阿霉素组的生长抑制作用更为显著(P<0.05);72 h后单独使用阿霉素组和阿霉素联合吲哚美辛组细胞早期凋亡率均增加(P<0.01),但阿霉素联合吲哚美辛组较阿霉素组凋亡率上升更为明显(P<0.05);RT-PCR和Western blot证实吲哚美辛能够下调ABCG2、MDR1和MRP1的表达(P<0.05)且呈现出浓度依赖性。提示吲哚美辛能够增强阿霉素对胶质瘤U251细胞的生长抑制作用,其机制与吲哚美辛下调耐药基因的表达有关。
Nonsteroidal anti-inflammatory tumor cells. In this experiment, indomethacin with drugs （NSAIDs） can enhance cell toxicity of chemotherapy on 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 ~tmol/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 ~tmol/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 ~tmol/L indomethacin combined with 0.8 mg/L adriamycin for72 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.
出处
《中国细胞生物学学报》
CAS
CSCD
北大核心
2013年第5期649-654,共6页
Chinese Journal of Cell Biology
关键词
胶质瘤
吲哚美辛
阿霉素
耐药基因
glioma
indomethacin
adriamycin
drug-resistance gene
