组蛋白去乙酰化酶抑制剂对宫颈癌细胞的放射增敏作用

Radiosensitizing activity of SAHA on cervical cancer cells

目的探讨组蛋白去乙酰化酶抑制剂SAHA对宫颈癌SiHa细胞的毒性和放射增敏作用。方法 2009年10月至2010年6月在河北联合大学医学院采用MTT法检测SAHA对SiHa细胞的毒性并计算IC50。选择20%IC50的SAHA与放疗联合,克隆形成实验分析SAHA对SiHa细胞的放射增敏作用,采用Sigma Plot 2000 Demo版软件,利用多靶单击模型S=1-(1-eD0/D)n拟合细胞存活曲线,计算放射相关参数和放射增敏比,评价增敏效果。结果 MTT结果显示SAHA对SiHa细胞的毒性反应呈浓度和时间依赖性,SAHA作用SiHa细胞48h的IC50为4.80μmol/L。克隆形成实验结果显示,SAHA联合放疗组细胞的克隆形成率明显低于单独放疗组,二者的平均致死剂量(D0)分别为2.329、1.213,准阈剂量Dq分别为1.721、0.823。放射增敏比(SER)为1.92。结论 SAHA对宫颈癌SiHa细胞有良好的细胞毒性和放射增敏作用。

Objective To observe the radiosensitivity effect of histone deacetylase inhibitor SAHA on human cervical cancer SiHa cells. Methods MTT assay was used to measure the proliferation inhibition of SAHA on SiHa cells from October 2009 to June 2010 in Medical College of Hebei United University. The radiosensitivity effects of SAHA on SiHa cells with the concentration of 20% of IC50 were evaluated by the clonogenic assay. The software Sigma Plot 2000 Demo and the multi-target click model S = 1 - （ 1 - eD0/D） n was used to fit cell survival curve, determining radiation-related i parameters and sensitive enhancement ratio （SER） to evabaate of sensitizing effect. Results ＇ MTr results showed that toxicity of SAHA on SiHa cell was in a dose and time dependent manner. The IC50 of the proliferation inhibition of SAHA on SiHa cells was 4. 80txmol/L. Cloning experimental results showed that cell survival rate was lower after treatment with the combination of SAHA （20% of IC50） and radiation than the cell survival rate with radiation alone. Both~ the average lethal dose （DO） was 2. 329 and 1. 213 respectively, quasi-threshold dose （Dq） was 1. 721 and 0. 823 respectively. The sensitivity enhancement ratio （SER） was 1.92. Conclusion SAHA has a good cytotoxieity and radiosensitization on Si. Ha cell.