榄香烯对人胶质瘤U251细胞的放射增敏机制

目的:探讨榄香烯对人胶质瘤U251细胞的放射增敏机制。方法:以U251细胞系为离体胶质瘤模型,用不同浓度榄香烯和不同放射剂量分别处理U251细胞,采用MTT实验检测细胞活力,流式细胞术检测细胞凋亡及细胞周期,Western blot检测相关蛋白的表达水平。结果:榄香烯对U251细胞具有生长抑制及放射增敏作用;放疗联合榄香烯组U251细胞较放射组有更高的早期凋亡率、继发性坏死率和总死亡率;榄香烯能诱导U251细胞G₂/M期阻滞;榄香烯通过降低细胞分裂周期蛋白2(Cdc2)表达,导致放疗诱导的cyclin B1表达降低,从而抑制cyclin B-Cdc2复合物形成;同时抑制Cdc2蛋白第161位苏氨酸磷酸化,降低Cdc2的活性,从而诱导细胞G₂/M期阻滞;另外可能通过下调survivin表达,介导细胞凋亡。结论:榄香烯可能通过下调Cdc2蛋白、降低cyclin B1表达、抑制cylcin B-Cdc2复合物的形成、下调survivin表达等方面增强U251细胞对放疗的敏感性。

Mechanism of elemene enhancing radiosensitivity of human glioma U251 cells

AIM:To investigate the effect of elemene on the radiosensitivity of human glioma U251 cells and its mechanism.METHODS:The U251 cells were used as a glioma model in vitro,and were exposed to different concentrations of elemene and different doses of radiation.The cell viability was measured by MTT assay,the apoptosis and cell cycle distribution were analyzed by flow cytometry,and the related protein levels were determined by Western blot.RESULTS:Elemene inhibited the viability of U251 cells in vitro and enhanced the radiosensitivity of the cells.The cells in radiotherapy combined with elemene group had higher rates of early apoptosis,secondary necrosis and total cell death than those in radiation group.Elemene induced G2/M phase arrest in the U251 cells.Elemene reduced the protein expression of cell division cycle protein 2(Cdc2),which resulted in the decrease in cyclin B1 expression induced by radiotherapy,thereby inhibiting the formation of cyclin B-Cdc2 complex.Elemene reduced Cdc2 activity by inhibiting the phosphorylation of Cdc2 protein at threonine 161,thereby inducing G2/M phase arrest in the cells.It also mediated apoptosis by downregulating survivin expression.CONCLUSION:Elemene may increase the sensitivity of U251 cells to radiotherapy by down-regulating Cdc2 protein,decreasing cyclin B1 expression,inhibiting the formation of cylcin B-Cdc2 complex and down-regulating the expression of survivin.