尼莫地平对C6胶质瘤离体细胞及荷瘤大鼠替尼泊苷浓度的影响研究

Effect of Nimodipine on Concentration of Teniposide in ex Vivo C6 Glioma Cell and Tumor-Bearing Rat

目的探讨尼莫地平(Nim)对胶质瘤细胞及荷瘤大鼠替尼泊苷(Ten)的浓度及药效学的影响。方法 WST-1法测定Ten的IC50和Nim的安全浓度,选用此浓度进行实验,判断药物合用是否有协同作用。分为单独应用Ten和联用Nim组,体外细胞采用溶涨法破膜,测定细胞液内Ten的浓度;荷瘤大鼠测定血浆和脑组织中Ten的浓度,Ten含量测定采用HPLC-MS/MS。结果联合应用Nim的C6细胞用药48h细胞液中Ten的浓度是单独用药的10倍以上,荷瘤大鼠测定血浆浓度联合用药为155.02μg·L-1,单独用药为72.25μg·L-1。正常脑组织部分浓度相差不大。结论 Nim可明显增加细胞内和荷瘤大鼠血浆中化疗药物Ten的浓度,明显增强抗肿瘤作用。为临床胶质瘤病人联合用药提供理论依据。

OBJECTIVE To investigate the effects of nimodipine on the teniposide concentration in glioma cells and in the tumor-bearing rats,as well as teniposide pharmacodynamics. METHODS The IC50 of teniposide and the safe concentration of nimodipine were determined by WST-1 method. Under the concentration,the synergistic effect of the drug combination was evaluated. The glioma cells and tumor-bearing rats were divided into two groups treated with teniposide and teniposide with nimodipine,respectively. Cell membrane swelling method was used to get the intracellular fluid of glioma cells. Then,the concentration of teniposide inside the glioma was detected by HPLC-MS/MS method. And the concentrations in glioma tumor-bearing rat plasma and brain tissue were determined in the same way. RESULTS The concentration of teniposide combined with nimodipine in glioma was as 10 times as that of group treated with teniposide alone at 48 h after the treatment. The plasma concentration of tumor-bearing rats in the group treated with nimodipine and teniposide was 155.02 μg·L-1 while the concentration in group treated with teniposide was 72.25 μg·L-1.The concentrations in normal brain tissue were different. CONCLUSION Nimodipine can markedly increase the teniposide concentration in glioma cells and in the plasma of tumor-bearing rat,improve the anti-tumor effects. This study provided an evidence for clinical drug combination for glioma patients.