Curcumin downregulation of MGMT expression to enhance the chemosensitivity of temozolomide on maligant glioblastoma / 国际肿瘤学杂志

ABSTRACT

Objective To explore the roles of curcumin in regulating high level O6-methylguanine-DNA methyltransferase (MGMT) expression and the chemosensitivity of gliomas cells to temozolomide (TMZ) in malignant gliomas.Methods The expressions of MGMT were detected in C6 and U87 cell lines and primary malignant gliomas cell by qRT-PCR.The cell proliferation was analyzed after added in signal curcumin,signal TMZ,curcumin combined with TMZ in cells by CCK-8 assay.The cell apoptosis rate was detected by flow cytometry.Results Compared with single curcumin (C60.64 ±0.03;U870.63 ±0.06;primary cell0.51 ±0.07) and single TMZ (C60.53 ±0.06;U870.51 ±0.04;primary cell0.79 ±0.03),curcumin combined with TMZ (C60.14 ±0.01;U870.12 ±0.03;primary cell0.29 ±0.02) could significantly reduce the expression of MGMT in C6,U87 cell lines and primary cell line (C6F=23.675,P=0.006;U87F=29.021,P=0.001;primary cellF=25.534,P=0.001).The combination of curcumin and TMZ could significantly inhibit the cells proliferation,decrease the halfinhibition concentration (IC5o) value (C6F=6.731,P=0.012;U87F=17.321,P=0.008;primary cellF=18.857,P =0.007).The apoptosis rate of the cells was significantly increased after the combined action of curcumin and TMZ (C5F=25.871,P=0.001;U87F=6.847,P=0.009;primary cellF=36.641,P=0.000).Conclusion Synergistic effect of curcumin and TMZ can reduce the expression of MGMT and increase the chemosensitivity of TMZ to malignant glioma,and provide new strategy and methods for the treatment of malignant glioma.