β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1.
β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1.
复制标题
DOI：
10.5966/sctm.2016-0009
复制
发表时间：
2017-03
影响因子：
6
通讯作者：
Chen ZP
中科院分区：
文献类型：
--
作者：
Feng HB;Wang J;Jiang HR;Mei X;Zhao YY;Chen FR;Qu Y;Sai K;Guo CC;Yang QY;Zhang ZP;Chen ZP
胶质瘤是最常见的原发性中枢神经系统肿瘤。虽然目前的一线药物替莫唑胺（TMZ）可以促进患者生存，但耐药性很容易发展。因此，重要的是研究新的治疗试剂以巩固治疗效果。β-榄香烯（bELE）是一种来自中草药的化合物，其抗癌作用已在各种类型的癌症中显示。然而，其在抑制胶质瘤干细胞样细胞（GSLCs）中的作用尚未报道。我们研究了bELE和TMZ在体外和体内对GSLCs和亲本细胞的抑制作用以及它们的联合作用。分子机制也进行了研究。我们还优化了bELE的交付方式。我们发现bELE选择性地抑制GSLCs的增殖和球体形成，而不是亲本胶质瘤细胞，TMZ对亲本细胞而不是GSLCs发挥其作用。体内实验结果证实，bELE和TMZ的组合在GSLCs的异种移植物中发挥更好的作用，模拟了人类癌症的肿瘤发生情况。Notch 1在bELE处理后下调。我们的数据还表明，连续施用bELE产生控制肿瘤进展的理想效果。我们的研究结果首次证明，bELE可以补偿TMZ杀死GSLCs和非干细胞样癌细胞，可能极大地改善胶质瘤患者的预后。Notch 1可能是bELE的下游靶点。因此，我们的数据揭示了通过bELE和TMZ的组合来改善胶质瘤患者的预后。干细胞转化医学2017;6：830-839
Glioma is the most frequent primary central nervous system tumor. Although the current first‐line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β‐Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem‐like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem‐like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ. Stem Cells Translational Medicine 2017;6:830–839