联合使用针对不同亚群胶质母细胞瘤细胞的药物治疗协同抑制肿瘤生长。

Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells.

机构信息

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Department of Diagnostic Radiology, National Cheng Kung University Hospital, Tainan, Taiwan.

出版信息

BMC Cancer. 2017 Dec 29;17(1):905. doi: 10.1186/s12885-017-3924-y.

BACKGROUND

Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133 cells and their sensitivity to pharmacological inhibition.

METHODS

GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a cancer stem cell marker. Cell proliferation was determined using the WST-1 assay. An intracranial mouse model and bioluminescence imaging were used to assess the effects of drugs on tumor growth in vivo.

RESULTS

CD133 cells expressed stem cell markers and exhibited self-renewal and enhanced tumor formation. Minocycline (Mino) was more effective in reducing the survival rate of CD133 cells, whereas CD133 cells were more sensitive to inhibition by the signal transducer and activator of transcription 3 (STAT3) inhibitor. Inhibition of STAT3 decreased the expression of CD133 stem cell markers. The combination of Mino and STAT3 inhibitor synergistically reduced the cell viability of glioma cells. Furthermore, this combination synergistically suppressed tumor growth in nude mice.

CONCLUSION

The results suggest that concurrent targeting of different subpopulations of glioblastoma cells may be an effective therapeutic strategy for patients with malignant glioma.

背景

神经胶质瘤干细胞（GSCs）有助于肿瘤复发和耐药。本研究对 CD133 细胞的肿瘤发生及其对药理抑制的敏感性进行了特征描述。

方法

通过使用 CD133 作为癌症干细胞标志物的磁细胞分选，从人 U87 和大鼠 C6 神经胶质瘤细胞系中分离 GSCs。通过 WST-1 测定法测定细胞增殖。使用颅内小鼠模型和生物发光成像来评估药物对体内肿瘤生长的影响。

结果

CD133 细胞表达干细胞标志物，并表现出自更新和增强的肿瘤形成能力。米诺环素（Mino）在降低 CD133 细胞存活率方面更有效，而 CD133 细胞对信号转导和转录激活因子 3（STAT3）抑制剂的抑制更为敏感。抑制 STAT3 降低了 CD133 干细胞标志物的表达。米诺环素和 STAT3 抑制剂的联合使用可协同降低神经胶质瘤细胞的活力。此外，该联合疗法还可协同抑制裸鼠的肿瘤生长。