诱导分化剂联合化疗药治疗可移植性人脑胶质瘤的实验研究

Combination Therapy for Human Glioma Xenograft with Differentiation-inducing Agent and Chemotherapeutic Drug

背景与目的:丙戊酸钠(valproate,VPA)不仅是经典的临床抗癫痫药物,近年来还发现其对多种肿瘤细胞都有一定的诱导分化作用,但单独应用或与化疗药联合应用对脑胶质瘤体内疗效如何尚不确定。本研究旨在探讨两者抗胶质瘤的联合效应。方法:将低分化人脑胶质瘤体外细胞系SHG-44移植于裸小鼠制作成可移植性实体瘤模型后,单用VPA以及联合应用盐酸尼莫司汀(nimustine,ACNU)进行治疗,观察移植瘤体积、病理学形态、细胞增殖周期、分化抗原表达等指标的变化。结果:VPA和ACNU联合用药组的疗效明显优于任何一种单独给药组,表现为肿瘤生长抑制,细胞异型性降低,G0/G1期细胞比例增加,胶原纤维酸性蛋白表达上调。结论: VPA联合应用化疗药能够明显增强VPA抑制人脑胶质瘤生长和诱导其向良性分化的作用。

BACKGROUND & OBJECTIVE: Valproate(VPA) is a well established drug in the longterm therapy of epilepsy. Recently, it has been evidenced that VPA can induce kinds of tumor cells to differentiate. However, the therapeutic effect of VPA alone and combined with chemotherapeutic drug on brain glioma in vivo has not been evaluated. This study was designed to investigate the associated effects of VPA and chemotherapeutic drug for gliomas. METHODS: Lower-differentiated human glioma cell line SHC-44 xenografted nude mice was treated with VPA alone or VPA with Nimustine(ACNU). The therapeutic effects were determined by measuring tumor size, pathological change, different phase of cell cycle of tumor cell proliferation, expression of differentiation antigen. RESULTS:The therapeutic effects of VPA plus ACNU group was much better than that of VPA or ACNU alone, which demonstrated by lower growth rate of tumor, cellularity decreasing, G0/G1 phase ratio increasing, upregulation of glial fibrillary acidic protein (GFAP) expression. CONCLUSION:VPA combined with chemotherapeutic drug can obviously enhance the proliferative inhibition of glioma and promote the effect of differentiation to benign.