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背景与目的:从胶质瘤中分离的肿瘤干细胞(cancer stem cells,CSCs)是胶质瘤的种子细胞和复发的源泉,它们不能被有效的杀死导致胶质瘤的预后不理想。本研究旨在探讨胶质瘤来源的肿瘤干细胞对化疗药物的耐药性及相关耐药酶的表达。方法:用免疫磁珠法从U251细胞中分选肿瘤干细胞(U251-CSC)后继续培养;MTT比色试验法观察化疗药物替尼泊苷(Vm-26)、卡莫司汀(BCNU)和顺铂(DDP)对U251和U251-CSC的增殖抑制作用,流式细胞仪检测3种化疗药物引起的细胞凋亡;Western blot免疫印迹法检测3种耐药酶LRP、MGMT和TopoⅡα的表达。结果:在3种药物作用下,U251的生长抑制比U251-CSC明显,U251的细胞凋亡率高于U251-CSC;U251-CSC表达LRP、MGMT和TopoⅡα的强度高于U251。结论:胶质瘤肿瘤干细胞对化疗药物Vm-26、BCNU和DDP有高耐药性,原因可能是肿瘤干细胞高表达耐药酶LRP、MGMT和TopoⅡα。
BACKGROUND & OBJECTIVE: Cancer stem cells (CSCs) isolated from glioma are the seed cells and source of recurrence of glioma. They can not be effectively killed and the prognosis of glioma is not ideal. This study aimed to investigate the drug resistance of glioma-derived cancer stem cells to chemotherapeutic drugs and the expression of drug-resistant enzymes. Methods: Tumor stem cells (U251-CSC) were sorted by UUF-1 cells using immunomagnetic beads method and then cultured. MTT colorimetric assay was used to observe the effects of chemotherapeutic drugs such as tenoposide (Vm-26), carmustine The inhibitory effects of DDP on the proliferation of U251 and U251-CSC were detected by flow cytometry. The expressions of LRP, MGMT and TopoⅡα were detected by Western blotting. Results: Under the action of three drugs, the growth inhibition of U251 was more obvious than that of U251-CSC and the apoptosis rate of U251 was higher than that of U251-CSC. The expression of LRP, MGMT and TopoⅡα in U251-CSC was higher than U251. Conclusion: Glioma tumor stem cells are highly resistant to chemotherapeutic agents Vm-26, BCNU and DDP. The reason may be that LRP, MGMT and TopoⅡα are highly expressed in cancer stem cells.