核因子NF-κB抑制剂PDTC对胶质瘤干细胞放疗增敏的效用研究

Effects of Nuclear Factor NF-κB Inhibitor PDTC on Radiosensitization of Glioma Stem Cells

目的 探讨核因子-κB(NF-κB)抑制剂四氢化吡咯二硫代氨基甲酸酯(PDTC)对胶质瘤干细胞放射治疗增敏的效用。方法 用无血清悬浮培养法培养胶质瘤干细胞,培养后,将细胞分成C组(加二甲基亚砜30μmol/L)、PDTC组(30μmol/L,加PDTC)、放疗组(8 Gy,加二甲基亚砜30μmol/L)和PDTC联合放疗组。采用Western blot比较各组放疗后36 h、48 h、72h胶质瘤干细胞中NF-κB蛋白表达及细胞凋亡情况。结果 X线照射后,胶质瘤干细胞中NF-κB蛋白表达明显增加,与C组比较差异有显著性(P<0.05),而PDTC可下调NF-κB蛋白表达,差异有统计学意义(P<0.05)。PDTC组、放疗组和联合组的胶质瘤干细胞凋亡率与C组比较,依次半圆(1.50±0.16)倍、(2.48±0.15)倍、(6.55±0.24)倍。结论 NF-κB通路在胶质瘤干细胞的放射治疗中起关键作用,并可以作为对胶质瘤干细胞放疗增加敏感性的重要靶点。

Objective To explore nuclear factor-κB(NF-κB)Effect of inhibitor tetrahydropyrrole dithiocarbamate(PDTC)on radiosensitization of glioma stem cells.Methods Glioma stem cells were cultured by serum-free suspension culture.After culture,the cells were divided into group C(30 μmol/L dimethyl sulfoxide),PDTC group(30 μmol/L),radiotherapy group(8 Gy,30 μmol/L dimethyl sulfoxide)and PDTC combined radiotherapy group.NF in glioma stem cells at 36 h,48 h and 72 h after radiotherapy were compared by Western blot NF-κB protein expression and apoptosis.Results After X-ray irradiation,The expression of NF-κB protein increased significantly compared with group C(P<0.05),and PDTC could down regulate NF-κB There was significant difference in the expression of NF-κB protein(P<0.05).Compared with group C,the apoptosis rates of glioma stem cells in PDTC group,radiotherapy group and combined group were semicircular(1.50±0.16),(2.48±0.15)and(6.55±0.24)times.Conclusion NF-κB pathway plays an important role in the radiotherapy of glioma stem cells,and can be used as an important target to increase the sensitivity of glioma stem cells to radiotherapy.