紫杉醇对骨肉瘤细胞放射增敏作用的研究

目的观察体外环境下紫杉醇对骨肉瘤（osteosarcoma,OS）细胞的放射增敏效果及其与药物作用时间的关系。方法以MG-63细胞为实验对象,采用MTT法检测不同浓度紫杉醇（6、0.6、0.06、0.006和0.000 6μg/mL）对MG-63细胞的抑制作用,确定IC10作为后续实验的药物浓度;采用克隆形成分析法分别测定MG-63细胞在紫杉醇作用24h后照射以及单纯照射的存活分数（SF）,拟合细胞生存曲线并计算放射增敏比,分析紫杉醇对MG-63细胞的放射增敏作用;采用克隆形成分析法测定紫杉醇作用于MG-63细胞12、24和36h后细胞生存率的变化,确定最佳照射时间。组间比较采用单因素方差分析。结果 MTT实验结果显示,当紫杉醇浓度分别为0.000 6、0.006、0.06、0.6和6μg/mL时,其细胞抑制率分别为（3.25±2.58）%、（9.98±3.83）%、（20.35±3.91）%、（21.55±3.70）%和（55.36±4.67）%。提示,紫杉醇对MG-63细胞的生长抑制作用呈浓度依赖性,F=83.70,P〈0.01,IC10为0.01μg/mL;IC10浓度紫杉醇増敏比分别为1.14（D0比）、1.20（Dq比）和1.08（SF2比）;MG-63细胞α/β值为2.23,IC10浓度紫杉醇作用后α/β值为2.32。紫杉醇作用于MG-63细胞12、24和36h后再进行照射,细胞存活分数分别为（9.21±0.81）%、（5.39±0.75）%和（0.38±0.13）%,显著低于对照组的（12.86±1.07）%,差异有统计学意义,F=144.11,P〈0.01。结论紫杉醇对MG-63细胞有放射增敏作用,增敏作用呈时间依赖性,有一定的临床应用前景。

Radiosensitization of paclitaxel on osteosarcoma cells in vitro

OBJECTIVE To explore the radiosensitization of paclitaxel on human osteosarcoma cells and relationship between radiosensitization and drug effect time in vitro. METHODS A human osteosarcoma cell line MG-63 was used in this study. MTT was used to investigate the cytotoxicity of paclitaxel and define the IC10 for MG-63 cells. Clonogenic assay was used to determine cell survival fractions of MG-63 ceils received radiation alone and paclitaxel administrated before irradiation. The cells treated with paclitaxel for 12, 24 and 36 hours before irradiation were used to evaluate the radiosensitization of paclitaxel by clonogenic assay to determine the best irradiation time. Comparisons of different groups were performed using one-way ANOVA. RESULTS MTT assay showed the cell inhibition rates were （3. 25 ± 2. 58）%, （9.98±3.83） %, （20.35±3.91）%, （21.55±3.70） % and （55.36＋4.67） % respectively when paclitaxel treatment concentrations were 0. 000 6, 0. 006, 0.06, 0.6 and 6 μg/mL. The inhibiting effect was in a dose dependent manner, F= 83.70,P〈0. 01. The dose of IC10 of paclitaxel for MG-63 cells was 0.01 μg/mL. According to DO, Dq and SF2 value, the sensitivity enhancement ratios （SER） of MCr63 cells were 1.14（D0 rate）, 1.20（Dq rate） and 1.08（SF2 rate） when paelitaxel was added 24 hours before irradiation. The α/β value for MG-63 cells was 2.23 and became 2.32 after the cells were treated with paclitaxel. The survival fractions of MG-63 cells treated with paclitaxel for 12, 24 and 36 h before irradiation were （9.21±0.81） %, （5.39±0.75）% and （0.38!0. 13）% respectively, which were significantly lower than control group （12.86± 1.07） %, F= 144.11, P〈0. 01. CONCLUSIONS Moderate paclitaxel is able to enhance the radiation sensitivity of MG-63 cells. In a certain period of time it presents time dependent relation.