Enhanced MDR1 Expression and Chemoresistance of Cancer Stem Cells Derived from Glioblastoma
Enhanced MDR1 Expression and Chemoresistance of Cancer Stem Cells Derived from Glioblastoma
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DOI：
10.3109/07357900801946679
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发表时间：
2009-01-01
影响因子：
2.4
通讯作者：
Shimizu, Keiji
中科院分区：
文献类型：
--
作者：
Nakai, Eiichi;Park, Kaechang;Shimizu, Keiji
用神经干细胞培养液对胶质母细胞瘤(GBM)来源的U87 MG细胞进行球状培养，建立了肿瘤干细胞系U87CS。U87CS细胞多药耐药(MDR)1和CD133免疫组织化学染色阳性，CD133是白血病和GBM CS细胞亚群的标志。实时荧光定量RT-PCR检测显示，MDR1和CD133基因在U87CS细胞上的表达水平分别是U87 MG细胞的8.51倍和47.18倍。与U87 MG细胞相比，U87CS细胞对阿霉素(Dox)、依托泊苷(VP-16)、卡铂、BCNU等常规抗癌药物具有更强的耐药性。免疫荧光双重染色显示，裸鼠脑内移植的U87CS细胞同时表达MDR1和CD133。此外，我们还在一例GBM手术标本中鉴定了CD133和MDR1的交叉反应。我们的结果表明，CS细胞可能对当前的化疗具有抵抗力，并成为GBM治疗的新靶点。
We established a cancer stem (CS) cell line, U87CS, by means of spheroid culture of U87MG cells derived from glioblastoma (GBM) in neuronal stem cell medium. U87CS cells presented positive immunohistochemical staining for multidrug resistance (MDR)1 and CD133, a marker for a subset of leukemia and GBM CS cells. The gene expression of MDR1 and CD133 on U87CS cells increased by an average of 8.51 and 47.18 times, respectively, compared to the levels on U87MG cells by real-time quantitative RT-PCR. U87CS cells possessed stronger drug-resistance to conventional anti-cancer drugs, such as doxorubicin (Dox), etoposide (VP-16), carboplastin, and BCNU than U87MG cells. Double immunofluoresence staining showed co-expression of MDR1 and CD133 on U87CS cells transplanted into nude mice brains. In addition, we identified the crossreactivity of CD133 and MDR1 in a surgical specimen of GBM. Our results suggest that CS cells may be resistant to current chemotherapy and represent a novel target for GBM therapeutics.