摘要
目的为了阐明钙离子拮抗剂尼卡地平与表鬼臼毒噻吩糖甙(威猛VM26)联合作用逆转C6/VM26耐药、诱导胶质瘤细胞凋亡发生的机制。方法建立威猛对鼠胶质瘤C6细胞株对VM26的耐药模型,钙离子拮抗剂尼卡地平与威猛的协同作用,通过氚标记胸腺嘧啶脱氧核苷(3HTdR)掺入法检测抑制率和流式细胞仪检测凋亡峰。结果尼卡地平与威猛协同作用时,使威猛对C6/VM26的抑制率从33.45%提高到70.25%,与威猛组之间有显著差异(P<0.01),并使C6/VM26耐药细胞株产生了凋亡。结论尼卡地平与化疗药物竞争地结合肿瘤细胞膜上的p170糖蛋白,使化疗药物从细胞内泵出减少,细胞内药物积聚增多,增加了化疗药物的细胞毒性,逆转了耐药。同时通过干扰肿瘤细胞的有丝分裂,减少进入细胞周期的细胞数,使大量细胞在该时相堆积,因而不能完成DNA的复制和修复,细胞走向了凋亡。
Objective In order to elucidate the mechanism of resistance and apoptosis of Nicardipine （NCDP） combined with epipodophyllotoxin thenylidine （VM-26） reverse C6/VM-26. Methods A resistant model of C6 cell lines that was induced by VM-26 had been established. NCDP combined with VM-26 was detected by tritiate thymin deoxyrib-oside （3H-TdR） and flow cytometry. Remtlts When NCDP acted with VM-26, the cell inhibition ratio increased from 33.45% to 70.25% and induced apoptosis of cell lines. Comparing to VM-26 control, there was statistical significant difference （P 〈 0. 01 ）. Conclusion NCDP, a calcium channal blocker, can bind to the p-glycoprotein of cell membrane and block the binding of VM-26 to p-glycoprotein. This drug blocks the outside transport of antitumor agents, which leads to a high concentration of antitumor agents in resistant cells and thereby reverses the resistance. It interferes tumor cell split, destructed the DNA structure, decreases the quantity of cells in cell cycle, therefore the duplication and plerosis has not been completed with a result of cell apoptosis.
出处
《中华神经外科疾病研究杂志》
CAS
2005年第6期512-515,共4页
Chinese Journal of Neurosurgical Disease Research
