The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
Cancer Lett. 2011 Nov 28;310(2):148-59. doi: 10.1016/j.canlet.2011.06.029. Epub 2011 Jul 1.
Treatment of glioblastoma remains a challenge in neuro-oncology. We investigated if treatment with neural stem cells engineered to express membrane-bound TRAIL (NSCs-mTRAIL) alone or in combination with proteasome inhibitors is a feasible therapeutic approach for experimental glioma. Glioma cells showed resistance to soluble TRAIL and proteasome inhibitors alone, but responded well to their combined treatment. In co-culture with NSCs-mTRAIL, glioma cells appeared to be more prone to apoptosis than to treatment with soluble TRAIL, which was enhanced by proteasome inhibitor bortezomib. In vivo, the survival of animals bearing intracranial glial xenografts was significantly improved by NSCs-mTRAIL. The addition of bortezomib further enhanced the efficacy of NSCs-TRAIL treated group in one of examined tumor models. These data demonstrate that therapy with NSCs-mTRAIL is a potent cell based approach for treatment of glioma. Such an approach warrants further search for therapeutics capable of increasing sensitivity of glioma cells to mTRAIL in vivo.
胶质母细胞瘤的治疗仍然是神经肿瘤学的一个挑战。我们研究了工程化表达膜结合 TRAIL（NSCs-mTRAIL）的神经干细胞单独或与蛋白酶体抑制剂联合治疗实验性神经胶质瘤是否是一种可行的治疗方法。胶质母细胞瘤细胞对可溶性 TRAIL 和蛋白酶体抑制剂单独治疗具有耐药性，但对联合治疗反应良好。在与 NSCs-mTRAIL 的共培养中，与单独使用可溶性 TRAIL 相比，胶质母细胞瘤细胞似乎更容易发生凋亡，而硼替佐米等蛋白酶体抑制剂增强了这种作用。在体内，携带颅内胶质异种移植物的动物的存活率通过 NSCs-mTRAIL 显著提高。在检查的一种肿瘤模型中，硼替佐米的加入进一步增强了 NSCs-TRAIL 治疗组的疗效。这些数据表明，NSCs-mTRAIL 治疗是治疗神经胶质瘤的一种有效的基于细胞的方法。这种方法需要进一步寻找能够增加体内胶质母细胞瘤细胞对 mTRAIL 敏感性的治疗方法。
