尼卡地平和VM-26逆转C6/VM-26耐药性研究

目的阐明胶质瘤耐药发生的机制,克服耐药性的产生,提高手术后化疗的效果,增加胶质瘤细胞对化疗药物的敏感性,最大限度地抑制胶质瘤细胞增殖,延缓肿瘤复发.方法模拟临床的给药方法,利用VM-26(威猛)在不同条件下的诱导建立了鼠胶质瘤C6细胞株对VM-26的耐药模型,通过钙离子拮抗剂尼卡地平(NCDP)作用,提高了VM-26对耐药的C6细胞株的敏感性.结果利用尼卡地平(5 mg/L)与VM-26协同作用时,使VM-26对C6/VM-26的抑制率从33.45%分别提高到70.25%,与VM-26组之间有显著差异(P<0.01).结论尼卡地平通过与化疗药物竞争地结合肿瘤细胞膜上的P-170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,逆转耐药.

On Nicardipine Combining with VM-26 Reverse C6/VM-26 Resistence

Objective In order to elucidate the mechanism of the glioma resistance, overcome the current of resistance, improve the postoperation effect of chemotherapy and delay the recurrence of glioma. Methods The resistant model of C6 cell lines that is induced by VM 26 was established by the way of clinical administration. The sensitivity of VM 26 increased and its resistance is reversed by the cooperating of Nicardipine(NCDP).Results When NCDP act with VM 26, the cell inhibition ratio increase from 33.45% to 70.25%. There is statistical signification compared with VM 26 control( p <0.01). Conclusion NCDP, a calcium channel blocker, can bind to the cell membrane glucoprotein and block the binding of VM 26 to glucoprotein. This drug blocks the outside transport of antitumor agents, leads to a high concentration of antitumor agents in resistant cell and thereby reverse the resistance.