Abstract:

Objective  To investigate the effects of alone and combined administration of two natural drugs dihydroartemisinin (DHA) and triptolide (TP) on in vitro inhibition and in vivo treatment of glioma. Methods  CCK-8 method was adopted to detect the inhibitory effect of alone and combined administration of DHA and TP on the viability of glioma cells. Hochest 33258 staining was used to observe changes of cell nucleus after administration. Rhodamine123 and PI staining was adopted to detect the mitochondrial membrane potential and cell cycle. The transplanted tumor model of mice with glioma was established. The body weight and size of tumor were observed after administration and were statistically analyzed. Pathological sections of main organs were H-E stained and the in vivo toxicity of drugs was observed. Results  Alone and combined administration of DHA and TP of 12 μg/mL for treating glioma cells C6 and U87 for 48 h significantly inhibited the cell viability and inhibition rates were 85% and 80%, respectively. Alone and combined administration of DHA and TP could cause the karyopyknosis and significant decline of mitochondrial membrane potential. The decline of mitochondrial membrane potential caused by combined administration was more than that caused by alone administration (P<0.01). Combined administration of DHA and TP mainly arrested the cell cycle at Sub-G1 and G2/M phases. The results of in vivo tests suggested that combined administration could inhibit the growth of tumor more effectively than alone administration and controls (P<0.01). H-E stained pathological sections showed that combined administration had little in vivo toxicity. Conclusion  Combined administration of DHA and TP has significant synergetic inhibition effect on glioma cells and the in vivo therapeutic effect is also remarkable, which provides a new method for clinical treatment of glioma with natural drugs.

Key words: dihydroartemisinin, triptolide, drug combination, glioma, in vivo therapy, apoptosis