In Vivo Study On The Sensitization Mechanism Of Curcumin To Glioma Radiotherapy

Objective: To study of curcumin on human brain glioma cell line U87 radiotherapy sensitization effect and possible mechanism in vivo.Methods: 20 male aged 6-8 weeks BALB- c nude mice were randomly divided into four groups, each inoculated glioma U87 cell 5 ×106 / ml in the right side of the back under the skin, to receive oral curcumin alone(50 mg/kg every 2 days), irradiation alone(5 Gy every 2 days), curcumin + irradiation(curcumin was administered to the mice at 2 h prior to irradiation) or no treatment(control). Calculate the volume and weight of the transplanted tumor. PCR analysis with different treatment groups was used to investigate the relative expression of double specificity phosphatase- 2(DUSP- 2) from tumor tissue samples. Western blot analysis with different treatment group was used to investigate protein expression level of double specificity phosphatase- 2(DUSP- 2), the molecular pathways downstream of phosphorylated extracellular signal regulating kinase(p- ERK), ERK phosphorylation c- jun amino terminal kinase(p- JNK) and JNK. Immunohistochemical analysis with different treatment group was used to investigate positive points of the double specificity phosphatase- 2(DUSP- 2), ERK and JNK. Terminal deoxyribonucleotide transferase mediated d UTP Nick end labeling method(TUNEL) with different treatment groupswas used to detect apoptosis index.Result: Curcumin has to inhibit the action of the subcutaneous glioma. Curcumin combined with radiotherapy can significantly inhibit the growth of subcutaneous glioma model. Curcumin combined with radiotherapy group significantly raised double specificity phosphatase(DUSP- 2) m RNA transcription level. Curcumin combined with radiotherapy group significantly raised double specificity phosphatase(DUSP- 2) protein expression, significantly reduce the amount of p- ERK and p-JNK protein expression. Curcumin combined with radiotherapy group significantly enhanced DUSP- 2 positive expression capacity, significantly reduce the amount of positive expression of ERK and JNK. Curcumin combined with radiotherapy group significantly increased apoptosis.Conclusion: Curcumin has a remarkable effect on the radiotherapy sensitization of glioma in vivo. The mechanism may be related to the upregulation of DUSP-2 expression, and then inhibit the phosphorylation of ERK and JNK, and promote the apoptosis to enhance the radiotherapy sensitivity.