胶质母细胞瘤紫杉醇增敏放射的体外实验研究

In Vitro studies on radiosensitizing effect of taxol in glioblastoma

目的:通过体外实验评价紫杉醇对胶质母细胞瘤的放射增敏作用,方法:应用人脑胶质母细胞瘤细胞系BT 325.细胞暴露于不同浓度(1、10、100、1000nM)紫杉醇,分别于6、12、24、48、72 h收集细胞,作流式细胞术细胞周期分析;细胞经紫杉醇(10nM,24h)和/或照射(6Gy)处理后,培养5天,每日计数活细胞,绘制细胞生长曲线;细胞经紫杉醇和/或照射处理后,培养14天,计算出细胞存活率和10%存活率时的放射增敏比(SER).结果:细胞暴露于紫杉醇后发生了G_2-M期阻滞,当紫杉醇作用时间较长或浓度较高时,G_2-M期细咆的比率也较高;紫杉醇＋照射组的细胞生长受到显著抑制;1、10、100nM紫杉醇在10%存活率时的SER分别为1.1、1.9、3.0.结论:(1)紫杉醇能将细胞阻滞在对射线最敏感的G_2-M期,这可能是其放射增敏的机理之一;并且这种作用具有时间和浓度依赖性.(2)体外实验显示紫杉醇能增强胶质母细胞瘤的放射生物学效应,提示值得进一步研究.

Objective: To assess the radiosensitization properties of taxol in human glioblas-toma cell line in vitro. Methods: A human glioblastoma cell line, BT325, was used for this exper-iment. 1. Cells were exposed to taxol at different concentrations (1, 10, 100, 1000 nM) for 6, 12,24,48, 72 h after which the cells were harvested. Cell cycle analysis was performed with flow cy-tometer. 2. The cells treated with taxol (10 nM, 24 h) or/and RT(6 Gy) were incubated for 5 d.The viable cells treated and untreated were counted each day, and cell growth curves were drawn.3. The cells treated with taxol (1, 10, 100, 1000 nM) or/and RT(2, 4, 6, 8, 10 Gy) were culturedin drug free media for 14 d, and colonies greater than 50 cells were counted. Surviving fraction(SF) and sensitizer enhancement ratios (SER) at 10% survival were evaluated. Results: Cells de-veloped a G2-M block after exposure to taxol. The percentage of the cell population in G2-M washigher at longer taxol exposure time and at higher taxol concentration. The cell growth for taxolplus RT was significantly inhibited. The SERs for 1, 10 and 100 nM taxol at 10% survival were1. 1, 1. 9 and 3. 0, respectively. Conclusion: 1. Taxol can bolck tumor cells in G2-M which arethe mostradiosensitive phases, being a likely mechanism of radiosensitization. 2. Taxol may be apromising radiosensiting agent for glioblastoma.