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目的探讨人脑胶质瘤细胞多药耐药性（ＭＤＲ）的形成规律及其耐药特性。方法采用长春新碱（ＶＣＲ）在体外对人脑胶质瘤ＢＴ３２５细胞持续诱导获得了表现为ＭＤＲ特征的人脑胶质瘤细胞模型．以ＭＴＴ法测定胶质瘤细胞增殖，透射电镜行超微结构研究，通过流式细胞仪，检测培养的胶质瘤细胞与３２例术后胶质瘤新鲜组织标本中Ｐ－糖蛋白的表达。结果耐药的胶质瘤细胞ＢＴ３２５／ＶＣＲ对长春新碱的耐受程度为其亲本细胞的２４倍，对阿霉素、威猛交叉耐药，对５－氟脲嘧啶敏感。透射电镜下见ＢＴ３２５／ＶＣＲ细胞常染色质明显，线粒体丰富，粗面内质网增多。研究表明ＢＴ３２５／ＶＣＲ表现为Ｐ－糖蛋白介导的典型ＭＤＲ。胶质瘤新鲜组织标本中，Ｐ－糖蛋白表达阳性率为３７５％（１２／３２），同肿瘤的恶性程度呈正相关（Ｐ＜０．０１）。结论长春新碱能够诱导人脑胶质瘤细胞产生Ｐ－糖蛋白介导的典型ＭＤＲ。胶质瘤中多药耐药基因产物Ｐ－糖蛋白表达的阳性率同肿瘤的恶性程度呈正相关。应用流式细胞仅能早期发现耐药细胞，具有临床推广价值。
Objective To investigate the formation and drug resistance of multi-drug resistance (MDR) in human glioma cells. Methods Human glioma cell line BT325 was induced continuously by vincristine (VCR) in vitro. Human glioma cell model with MDR characteristic was obtained. The proliferation of glioma cells was determined by MTT assay. The ultrastructure of glioma cells was examined by transmission electron microscopy. The expression of P-glycoprotein in freshly differentiated glioma cells and glioma cells was detected by flow cytometry. Results The drug-resistant glioma cells BT325 / VCR was 24 times more tolerant to vincristine than its parental cells, and was resistant to doxorubicin, mighty cross-resistance and to 5-fluorouracil. Under the TEM, BT325 / VCR cells showed obvious chromatin, abundant mitochondria and increased rough endoplasmic reticulum. Studies have shown that BT325 / VCR appears to be a P-glycoprotein-mediated typical MDR. The positive rate of P-glycoprotein expression was 375% (12/32) in newly diagnosed glioma tissues, which was positively correlated with the malignant degree of glioma (P <0.01). Conclusion Vincristine induces P-glycoprotein-mediated typical MDR in human glioma cells. The positive rate of P-glycoprotein expression in glioma was positively correlated with the malignancy of the tumor. Flow cytometry can only detect drug-resistant cells early, with clinical promotion value.