长春新碱诱导人脑胶质瘤细胞的耐药性

Drug resistance of human glioma cells induced by vincristine

本文报告以细胞周期特异化疗药长春新碱（ＶＣＲ）对人脑胶质瘤Ｕ２５１ＭＧ细胞进行体外分步诱导法造成细胞的耐药性。细胞集落实验表明，经ＶＣＲ诱导的胶质瘤细胞Ｕ２５１ＶＲ—４０在１０～４０ｎｇ／ｍＬＶＣＲ培养液中，其细胞形成相当率是未诱导组Ｕ２５１ＭＧ细胞的２～１３倍（Ｐ＜０．０１）。同时，耐ＶＣＲ的Ｕ２５１ＶＲ—４Ｑ细胞对阿霉素（ＡＤＭ）亦有交叉耐药性，但与卡氮芥（ＢＣＮＵ）无耐药性产生。另外，５ｕｇ／ｍＬ尼卡地平（ＮＣＤＰ）能使其反转成药敏细胞。诱导过程中还发现，Ｕ２５１ＭＧ胶质瘤细胞直接在高浓度ＶＣＲ（６０ｎｇ／ｍＬ培养液中被杀伤和发生明显形态变化后，仍有少数细胞在无化疗药培养环境７～１０天可以复苏并且再增殖。研究结果不仅表明ＶＣＲ诱导的胶质瘤细胞能够产生多药耐受性（ＭＤＲ），而且提示该胶质瘤细胞中可能还存在一种修复微管系统的抗药机理。

Chemotherapeutic resistance in U251MG human glioma cells was caused by the step-wise revulsion with a cell cycle specific agent vincristine(VCR)in vitro。 he cell cloning experimentdemonstrated that the colony-forming efficency of U251V￣R--40 cells induced stepwisely in VCR was2 to 13 folds that of U251MG cells without inducement,in cell culture with 10～40 ng/mL VCR(P<0.01 ).Simultaneously,the cross-resistance to adriamycin(ADM)and no resistance to BCNU wereappeared in U251V￣R--40 cells。 However,the resistance cells could be reversed into the drug--sensi-tive cells by 5.Oμg/mL nicardipine(NCDP).In addition,it was observed that some cells with mopho-logic change might resuscitate and remultiply in no drug culture for 10 days later,while most of cellswere killed after U251MG cells were incubated directly in higher dose of VCR(60 ng/mL).Thisstudy not only revealed that the glioma cells could produce multidrug resistance(MDR)after VCR in-ducement,but also suggested that another mechanism of drug resistance,which repaired microtublesystem,might be in the glioma cells。