Drug resistance and expression of drug-resistance enzymes in brain cancer stem cells isolated from U251 cell lines / 中国癌症杂志

ABSTRACT

Background and purpose: Cancer stem cells (CSCs) isolated from human glioma are cancer-initiating cells and sources of tumor recurrence in brain tumors. The poor outcome of glioma is because cancer stem cells can not be eradicated. This article was aimed to explore the resistance of CSCs to chemotherapeutic agents and expression of drug-resistance enzymes in glioma cancer stem cells. Methods: Cancer stem cells from U251 were isolated by using magnetic sorting. The proliferation inhibitory effects of Vumon-26 (Vm-26), bischloronitrosourea (BCNU) and diamminedichloroplatinum (DDP) on U251-CSC and U251 were examined by drug sensitivity testing in vitro (MTT assay) and the apoptosis rates were observed by flow cytometry. Western blot was performed to examine the expression of three drug-resistance enzymes including LRP, MGMT and Topo Ⅱα. Results: Chemotherapeutic agents had a more obvious inhibitory effect on U251 than U251-CSC, as well as higher apoptosis rates. LRP, MGMT and Topo Ⅱα expression were significantly higher in U251-CSC as compared to U251, Conclusion: Glioma stem cells showed strong capability of tumor's resistance to chemotherapeutic agents including Vm-26, BCNU and DDP. This resistance is probably contributed by the CD133 positive cell with higher expression of on LRP, MGMT and Topo Ⅱα.