The experimental research on anti-glioma with temozolomide, all-trans retinoic acid and radiotherapy

Abstract

Objective To investigate whether the collaborative application of temozolomide (TMZ), all-trans retinoic acid (ATRA) and radiotherapy can induce the apoptosis of U251 glioma cells and the molecular mechanism. Methods We detected the cell apoptosis rate of control group (100 μl nutrient solution), radiotherapy group (radiation dosage of 8 Gy), medicine group (TMZ 200 μmol/L+ ATRA 20 μmol/L) and combined group (radiation dosage of 8 Gy+ TMZ 200 μmol/L+ ATRA 20 μmol/L) by flow cytometry method. The protein expression of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) was detected by Western blotting. Results The apoptosis rate was (9.96±3.78)%, (37.35±5.36)%, (59.89±7.15)% and (69.35±8.25)% in control group, radiotherapy group, medicine group and combined group respectively. The apoptosis rate in combined group was higher than that in other groupsThese differences were more obvious (χ2=7 471.175, P=0.000; χ2=2 057.235, P=0.000; χ2=195.717, P=0.000). Combined group can up-regulate the protein expression of p38MAPK in contrast to control guoup, radiation group and medicine group. These differences were more obvious (t=46.000, P=0.000; t=10.150, P=0.000; t=4.266, P=0.013). Combined group can down-regulate the protein expression of NF-κB in contrast to control guoup, radiation group and medicine group. These differences were more obvious (t=36.380, P=0.000; t=30.090, P=0.000; t=68.620, P=0.000). Conclusion The combined use of TMZ, ATRA and radiotherapy can induce the apoptosis of U251 glioma cells probably by the upregulation of p38MAPK and downregulation of NF-κB. Key words: Glioma; Apoptosis; Temozolomide; All-trans retinoic acid; Radiotherapy; p38 mitogen-activated protein kinase; Nuclear factor-κB